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Modulating the Biological Processes and Glycolysis of Hepatocellular Carcinoma Cells by UBR7’s Suppression of Pyruvate Kinase PKM2 认领 引用
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作者 Bo Liu Xue Li 《BIOCELL》 SCIE 2026年第7期137-153,共17页
Background:As a key glycolytic enzyme,Pyruvate kinase M2(PKM2),which is highly expressed in cancer cells,promotes hepatocellular carcinoma(HCC)proliferation/metastasis.This research investigates the involvement of Ubi... Background:As a key glycolytic enzyme,Pyruvate kinase M2(PKM2),which is highly expressed in cancer cells,promotes hepatocellular carcinoma(HCC)proliferation/metastasis.This research investigates the involvement of Ubiquitin protein ligase E3 component N-recognin 7(UBR7)in HCC progression/glycolysis and its potential mechanisms.Methods:UBR7 expressions in HHL-5,Huh-7,and HepG2 cells were investigated using Quantitative Reverse Transcription Polymerase Chain Reaction andWestern Blot.Cell counting kit-8,clone formation experiment,scratch-wound assay,and transwell testing were conducted to assess the malignant biological behaviors of HepG2 and Huh-7 cells;the absorption level of glucose and generation levels of lactic acid and ATP were tested by assay kits.Huh-7 cells with stably overexpressed or knocked down UBR7 were inoculated into nude mice.Regular measurements were conducted on the tumor size,the tumors were isolated and weighed on the 35th day,and the glycolytic level in the tumor tissues was determined.Results:In HCC cells,UBR7 was significantly downregulated.Notably,UBR7 knockdown promoted HCC progression and glycolysis,increasing the viability of HepG2 and Huh-7 cells by 23%–24%(p<0.001),whereas UBR7 overexpression exerted the opposite inhibitory effects,resulting in a reduction of about 19%–31%in cell viability(p<0.001).UBR7 knockdown upregulated PKM2 expression in HCC cells,while UBR7 overexpression led to a marked reduction in PKM2 levels.Importantly,PKM2 overexpression partly abrogated the inhibitory impacts of UBR7 on HCC progression and glycolysis.In vivo experiments further demonstrated that UBR7 overexpression suppressed tumor growth and hindered glycolysis in nude mice.Conclusion:UBR7 suppressed PKM2 expression,thus hindering malignant biological progression and glycolysis in HCC,providing a potential therapeutic target for HCC treatment. 展开更多
关键词 Ubiquitin protein ligase E3 component N-recognin 7 pyruvate kinase M2 hepatocellular carcinoma glycolysis
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Nuclear translocation of pyruvate kinase M2 drives high glucose-induced angiogenesis in retinal endothelial cells via the HIF-1α axis 认领 引用
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作者 Tian-Yi Liu Ya-Jing Tian +6 位作者 Peng-Zhou Kuai Yi-Sheng Luo Cheng-Wei Duan Tian-Peng Chen Xiao-Le Wang Dong-Mei Zhang Xin Cao 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2026年第5期858-868,共11页
AIM:To investigate the role of pyruvate kinase M2(PKM2)in high glucose(HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis.METHODS:Human reti... AIM:To investigate the role of pyruvate kinase M2(PKM2)in high glucose(HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis.METHODS:Human retinal microvascular endothelial cells(HRMECs)were cultured and divided into the following groups:normal glucose(NG,5.5 mmol/L),HG(30 mmol/L),HG with PKM2 knockdown(HG+shPKM2),and HG treated with the pharmacological activator TEPP‑46(HG+TEPP‑46).Cellular viability,proliferation,migration,and tube‑forming ability were assessed using CCK‑8,EdU,wound healing/Transwell,and Matrigel assays,respectively.The expression levels of PKM2,phosphorylated PKM2(p‑PKM2,Y105),hypoxia-inducible factor-1α(HIF‑1α),and vascular endothelial growth factor A(VEGFA)were detected by Western blotting.The oligomerization status of PKM2 was analyzed via native gel electrophoresis.The subcellular localization of PKM2 was examined by immunofluorescence and nuclear‑cytoplasmic fractionation.RESULTS:Under HG stimulation,the expression level of PKM2 was significantly increased(P<0.05).Knockdown of PKM2 was found to markedly suppress cell viability,proliferation,migration,and tube formation in HRMECs(P<0.05).Mechanistic studies revealed that phosphorylation of PKM2 at the Y105 site was promoted by HG treatment,which induced its dissociation from a tetramer to a dimer,thereby driving its nuclear translocation.Upon entering the nucleus,PKM2 was shown to exert critical non‑metabolic functions;it was physically bound to HIF‑1αand acted as its co‑activator,leading to significant upregulation of VEGFA expression(P<0.05).In contrast,the PKM2 activator TEPP‑46 effectively prevented dimerization and nuclear translocation of PKM2 by promoting its tetramerization.Consequently,the PKM2/HIF‑1αaxis‑mediated upregulation of VEGFA was blocked,ultimately resulting in the reversal of HG‑induced angiogenesis.CONCLUSION:HG influences retinal endothelial cell function by inducing PKM2 phosphor ylation,dimerization,and nuclear translocation.The shift in PKM2 phosphorylation and oligomerization status represents a key mechanism through which TEPP-46 reverses HGinduced angiogenesis. 展开更多
关键词 retinal endothelial cells glucose angiogenesis nuclear translocation pyruvate kinase M2 hypoxia-inducible factor-1α
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Exploring the mechanism of Shenhua tablet(肾华片)alleviating renal injury by regulating macrophage glycolysis via hypoxia-inducible factor-1α/pyruvate kinase M2 signaling pathway in diabetic kidney disease mice 认领 引用 被引量：1
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作者 CHEN Yuanchun JING Jiaxing +5 位作者 LI Qingmin ZHOU Xiaohong JIN Xiaofei GAO Weijuan CHEN Xiangmei YU Wentao 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2025年第3期528-537,共10页
OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-... OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-inducible factor-1α(HIF-1α)and pyruvate kinase M2(PKM2)signaling pathway,along with the glycolysis metabolism pathway.METHODS:The animals were divided into the following groups:Model,Control,dapagliflozin,SHT low-dose,SHT medium-dose,and SHT high-dose.We assessed 24-hour urine protein(24 h-UTP)levels,urinary albuminto-creatinine ratio,and regularly monitored fasting blood glucose during the treatment period.After treatment,we examined renal tissue structure,renal function(urea nitrogen,uric acid,creatinine,cystatin C,β2-microglobulin),and glycolysis in renal macrophages.Additionally,we observed macrophage polarization in renal tissue and measured inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10,monocyte chemoattractant protein-1)to assess the immunoinflammatory status of the renal tissue.Finally,we investigated the expression of the HIF-1α/PKM2 signaling pathway in macrophages to explore its role in the glycolysis process.RESULTS:SHT shows a beneficial effect in treating DKD by reducing 24 h-UTP,regulating blood glucose levels,improving renal tissue structure,protecting renal function,inhibiting macrophage glycolysis,reducing macrophage transformation to the M1 state,and suppressing the expression of the HIF-1α/PKM2 signaling pathway.CONCLUSION:SHT may exert renoprotective effects by inhibiting macrophage glycolysis via the HIF-1α/PKM2 signaling pathway.This inhibition decreases macrophage M1 polarization and reduces immunoinflammatory injury in the renal tissue of DKD mice. 展开更多
关键词 diabetic kidney disease macrophages glycolysis hypoxia-inducible factor-1α pyruvate kinase M2 Shenhua tablet
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Mitochondrial pyruvate dehydrogenase phosphatase metabolism disorder in malignant tumors 认领 引用 被引量：1
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作者 YUFENG WANG HUIFENG DANG +5 位作者 QIANQIAN WANG SHUXIAO WU LEI HAN XU LUO YINGXIA TIAN HAILIN TANG 《Oncology Research》 SCIE 2025年第8期1861-1874,共14页
This review focuses on the metabolic issues related to mitochondrial pyruvate dehydrogenase phosphatase(PDP)in malignant tumors and its potential mechanisms.Recent research on tumor metabolic mechanisms has shown that... This review focuses on the metabolic issues related to mitochondrial pyruvate dehydrogenase phosphatase(PDP)in malignant tumors and its potential mechanisms.Recent research on tumor metabolic mechanisms has shown that PDP dysregulation is closely linked to metabolic reprogramming in tumor cells,and potentially promotes tumor.Research has comprehensively explored the structural-functional characteristics of PDP,its metabolic regulatory mechanisms,and its role in various types of malignant tumors.Nevertheless,several questions still exist regarding its potential mechanisms within acetylation,phosphorylation,hypoxia,immune infiltration,mitochondrial metabolism,drug resistance,oxidative phosphorylation,and tumor prognosis.This article intends to summarize the latest research,examine PDP’s potential as a therapeutic target,and propose future research directions to enhance cancer treatment strategies. 展开更多
关键词 Malignant tumors Mitochondria Pyruvate dehydrogenase phosphatase(PDP) Metabolism
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Genome-scale metabolic network model-guided genetic modification of Escherichia coli for pyruvate accumulation 认领 引用
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作者 LI Xuefei GUO Chaohao +4 位作者 TONG Wenyue YANG Sen LIU Xiaoyun LI Jingchen KANG Ming 《微生物学报》 CAS CSCD 北大核心 2025年第10期4374-4391,共18页
[Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a... [Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a guide,we simulated pyruvate production of E.coli,screened key genes in metabolic pathways,and developed gene editing procedures accordingly.We knocked out the acetate kinase gene ackA,phosphate acetyltransferase gene pta,alcohol dehydrogenase adhE,glycogen synthase gene glgA,glycogen phosphorylase gene glgP,phosphoribosyl pyrophosphate(PRPP)synthase gene prs,ribose 1,5-bisphosphate phosphokinase gene phnN,and transporter encoding gene proP.Furthermore,we knocked in the transporter encoding gene ompC,flavonoid toxin gene fldA,and D-serine ammonia lyase gene dsdA.[Results]A shake flask process with the genetically edited mutant strain MG1655-6-2 under anaerobic conditions produced pyruvate at a titer of 10.46 g/L and a yield of 0.69 g/g.Metabolomic analysis revealed a significant increase in the pyruvate level in the fermentation broth,accompanied by notable decreases in the levels of certain related metabolic byproducts.Through 5 L fed-batch fermentation and an adaptive laboratory evolution,the strain finally achieved a pyruvate titer of 45.86 g/L.[Conclusion]This study illustrated the efficacy of a gene editing strategy predicted by a genome-scale metabolic network model in enhancing pyruvate accumulation in E.coli under anaerobic conditions and provided novel insights for microbial metabolic engineering. 展开更多
关键词 Escherichia coli pyruvate genome-scale metabolic network model CRISPR-Cas9 adaptive laboratory evolution
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Glycolytic potential enhanced by blockade of pyruvate influx into mitochondria sensitizes prostate cancer to detection and radiotherapy 认领 引用 被引量：2
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作者 Huan Xu Junyi Chen +14 位作者 Zhi Cao Xi Chen Caihong Huang Jin Ji Yalong Xu Junfeng Jiang Yue Wang Guowang Xu Lina Zhou Jingyi He Xuedong Wei Jason Boyang Wu Zhong Wang Shancheng Ren Fubo Wang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2022年第9期1315-1333,共19页
Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogrammi... Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling,RNASeq,and tissue microarrays.Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells.Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa.Furthermore,the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro.Results:MPC was elevated in PCa tissue compared with benign prostate tissue,but decreased during cancer progression.The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation,thus increasing the sensitivity of PCa cells to 18F-PET/CT(SUVavg,P=0.016;SUVmax,P=0.03)and radiotherapy(P<0.01).This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway.Conclusions:Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue.This transient blockage sensitized PCa to both detection and radiotherapy,thus indicating that glycolytic potential is a novel mechanism underlying PCa progression.The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment. 展开更多
关键词 Glycolytic potential prostate cancer mitochondrial pyruvate carrier(MPC) mitochondria pyruvate influx diagnosis radiotherapy
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Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats 认领 引用 被引量：25
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作者 Zhi-Yong Yang Yan Ling +4 位作者 Tao Yin Jing Tao Jiong-Xin Xiong He-Shui Wu Chun-You Wang 《World Journal of Gastroenterology》 SCIE CAS 2008年第28期4546-4550,共5页
AIM:To investigate the effect of delayed ethyl pyruvate(EP)delivery on distant organ injury,survival time and serum high mobility group box 1(HMGB1)levels in rats with experimental severe acute pancreatitis(SAP).METHO... AIM:To investigate the effect of delayed ethyl pyruvate(EP)delivery on distant organ injury,survival time and serum high mobility group box 1(HMGB1)levels in rats with experimental severe acute pancreatitis(SAP).METHODS:A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats.Animals were divided randomly into three groups(n=32 in each group):sham group,SAP group and delayed EP treatment group.The rats in the delayed EP treatment group received EP(30 mg/kg)at 12 h,18 h and 30 h after induction of SAP.Animals were sacrificed,and samples were obtained at 24 h and 48 h after induction of SAP.Serum HMGB1,aspartate arninotransferase(AST),alanine arninotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)levels were measured.Lung wet-to-dry-weight(W/D)ratios and histological scores were calculated to evaluate lung injury.Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats.RESULTS:Delayed EP treatment significantly reduced serum HMGB1 levels,and protected against liver,renal and lung injury with reduced lung W/D ratios(8.22±0.42 vs 9.76±0.45,P〈0.01),pulmonary histological scores(7.1±0.7 vs 8.4±1.1,P〈0.01),serum AST(667±103 vs 1368±271,P〈0.01),ALT(446±91 vs 653±98,P〈0.01)and Cr(1.2±0.3 vs 1.8±0.3,P〈0.01)levels.SAP rats had a median survival time of 44 h.Delayed EP treatment significantly prolonged median survival time to 72 h(P〈0.01).CONCLUSION:Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP.EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome(MODS)in SAP patients. 展开更多
关键词 Severe acute pancreatitis Ethyl pyruvate High mobility group box 1 multiple organ dysfunction syndrome Survival time
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Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions 认领 引用 被引量：13
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作者 Yang-Hui Bi Wen-Qi Han +4 位作者 Ruo-Fei Li Yun-Jiao Wang Zun-Shu Du Xue-Jiang Wang Ying Jiang 《World Journal of Gastroenterology》 SCIE CAS 2019年第16期1936-1949,共14页
BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate de... BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells. 展开更多
关键词 Warburg effect Hepatic progenitor cell Signal transducer and activator of transcription 3 Pyruvate kinase M2 Liver precancerous lesion
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Pyruvate is a prospective alkalizer to correct hypoxic lactic acidosis 认领 引用 被引量：11
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作者 Ying Wang Ya Huang +3 位作者 Jing Yang Fang-Qiang Zhou Lian Zhao Hong Zhou 《Military Medical Research》 SCIE CAS 2018年第4期361-370,共10页
Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be ha... Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase(PDH) activator with several unique beneficial biological properties, including anti-oxidant and antiinflammatory effects and the ability to activate the hypoxia-inducible factor-1(HIF-1α)-erythropoietin(EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients. 展开更多
关键词 Type A lactic acidosis Hyperlactatemia Pyruvate Glucose metabolism PDH activator
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Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure 认领 引用 被引量：14
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作者 Li-Kun Wang Lu-Wen Wang +2 位作者 Xun Li Xiao-Qun Han Zuo-Jiong Gong 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2013年第2期180-188,共9页
BACKGROUND: The pathogenesis and progression of acute liver failure (ALF) are closely associated with intestinal endotoxemia because of the high permeability of the intestinal wall. Treatment with ethyl pyruvate (EP) ... BACKGROUND: The pathogenesis and progression of acute liver failure (ALF) are closely associated with intestinal endotoxemia because of the high permeability of the intestinal wall. Treatment with ethyl pyruvate (EP) has been shown to protect liver failure effectively. The current study aimed to explore the relationship between proinflammatory cytokines and intestinal permeability, and to investigate whether EP administration might prevent the release of multiple proinflammatory cytokines and decrease intestinal permeability and therefore, protect the liver from injury. METHODS: The ALF model was induced by D-galactosamine in rats. The rats were randomly divided into control (saline i.p.), model (D-galactosamine, 1.2 g/kg, i.p.), prevention [EP injection (40 mg/kg) 2 hours ahead of D-galactosamine] and treatment groups (EP injection 2 hours after D-galactosamine) Samples were obtained at 12 and 24 hours after ALF induction respectively. The histology of liver and intestinal tissue was accessed. Serum alanine aminotransferase, endotoxin, D(-) lactate, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and high mobility group box-1 (HMGB1) were evaluated. The survival of rats was also recorded. RESULTS: The rats in model group showed severe damage to liver tissue and intestinal mucosa 12 and 24 hours after ALF induction. EP significantly improved liver or intestinal injury In addition, serum endotoxin, D(-)-lactate, DAO, TNF-α IFN-γ and HMGB1 levels were significantly increased in the model group compared with the control group. There was a positive correlation between intestinal permeability andproinflammatory cytokines. EP significantly reduced serum endotoxin, D(-)-lactate, DAO, TNF-α, IFN-γ and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group). CONCLUSIONS: EP has protective and therapeutic effects on intestinal mucosa. EP decreases intestinal permeability, and inhibits the release of multiple proinflammatory cytokines in rats with ALF. 展开更多
关键词 acute liver failure ethyl pyruvate intestinal permeability cytokines
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Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer 认领 引用 被引量：5
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作者 Xu-Ren Sun Zhe Sun +8 位作者 Zhi Zhu Hai-Xia Guan Chen-Yan Li Jun-Yan Zhang Yi-Ning Zhang Huan Zhou Hui-Jing Zhang Hui-Mian Xu Ming-Jun Sun 《World Journal of Gastroenterology》 SCIE CAS 2015年第17期5336-5344,共9页
AIM:To investigate the expression and prognostic role of pyruvate dehydrogenase(PDH) in gastric cancer(GC).METHODS:This study included 265 patients(194 male,71 female,mean age 59 years(range,29-81 years) with GC who u... AIM:To investigate the expression and prognostic role of pyruvate dehydrogenase(PDH) in gastric cancer(GC).METHODS:This study included 265 patients(194 male,71 female,mean age 59 years(range,29-81 years) with GC who underwent curative surgery at the First Affiliated Hospital of China Medical University from January 2006 to May 2007.All patients were followed up for more than 5 years.Patient-derived paraffin embedded GC specimens were collected for tissue microarrays(TMAs).We examined PDH expression by immunohistochemistry in TMAs containing tumor tissue and matched nonneoplastic mucosa.Immunoreactivity was evaluated independently by two researchers.Overall survival(OS) rates were determined using the Kaplan-Meier estimator.Correlations with other clinicopathologic factors were evaluated by two-tailed χ2 tests or a two-tailed t-test.The Cox proportional-hazard model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis.RESULTS:Immunohistochemistry showed that 35.47% of total cancer tissue specimens had cytoplasmic PDH staining.PDH expression was much higher in normal mucosa specimens(75.09%;P = 0.001).PDH expression was correlated with Lauren grade(70.77% in intestinal type vs 40.0% in diffuse type;P = 0.001),lymph node metastasis(65.43% with no metastasis vs 51.09% with metastasis;P = 0.033),lymphatic invasion(61.62% with no invasion vs 38.81% with invasion;P = 0.002),histologic subtypes(70.77% in intestinal type vs 40.0% in diffuse type;P = 0.001) and tumor-node-metastasis(TNM) stage(39% in poorly differentiated vs 65.91% in well differentiated and 67.11% in moderately differentiated;P = 0.001) in GC.PDH expression in cancer tissue was significantly associated with higher OS(P < 0.001).The multivariate analysis adjusted for age,Lauren classification,TNM stage,lymph node metastasis,histological type,tumor size,depth of invasion and lymphatic invasion showed that the PDH expression in GC was an independent prognostic factor for higher OS(HR = 0.608,95%CI:0.504-0.734,P < 0.001).CONCLUSION:Our study indicated that PDH expression is an independent prognostic factor in GC patients and that positive expression of PDH may be predictive of favorable outcomes. 展开更多
关键词 Pyruvate dehydrogenase Gastric carcinoma Tissue microarray Prognosis Immunohistochemicalanalysis
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Effects of Ethyl Pyruvate on Myocardial Apoptosis and Expression of Bcl-2 and Bax Proteins after Ischemia-reperfusion in Rats 认领 引用 被引量：31
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作者 郭家龙 张凯伦 +2 位作者 季艳梅 蒋雄刚 左顺庆 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2008年第3期281-283,共3页
In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemiaeperfusion （I/R） in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff... In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemiaeperfusion （I/R） in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups （n=8 in each group）： control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate （EP） group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 rain before ischemia and throughout reperfusion. Myocardial malonaldehyde （MDA） content was measured. Myocardial apoptotic index （AI） was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group （P〈0.05）. These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins. 展开更多
关键词 ethyl pyruvate myocardial reperfusion injury apoptosis Bcl-2 protein Bax protein
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Tumor pyruvate kinase M2:A promising molecular target of gastrointestinal cancer 认领 引用 被引量：3
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作者 Chen Guo Guan Li +4 位作者 Jianing Hou Xingming Deng Sheng Ao Zhuofei Li Guoqing Lyu 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2018年第6期669-676,共8页
Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinas... Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinase isoform M2(PKM2),a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate(PEP) to pyruvate,confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment.In this review,we have summarized current research on the expression and regulation of PKM2 in tumor cells,and its potential role in GI carcinogenesis and progression.Furthermore,we have also discussed the potential of PKM2 as a diagnostic and screening marker,and a therapeutic target in GI cancer. 展开更多
关键词 PKM2(pyruvate kinase M2) metabolic reprogramming gene transcription gastrointestinal cancer therapy targets
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Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer 认领 引用 被引量：23
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作者 Jae Yun Lim Sun Och Yoon +4 位作者 So Young Seol Soon Won Hong Jong Won Kim Seung Ho Choi Jae Yong Cho 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第30期4037-4043,共7页
AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric c... AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment.Clinical and pathological information were obtained from the medical records.Gene expression microarray data from 60 cancer and 19 noncancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA.Tissue microarrays were constructed from 368 gastric cancer patients.Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity.Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS:PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients(log transformed expression level:7.6 ± 0.65 vs 6.3 ± 0.51,P < 0.001).Moreover,differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers(log transformed expression level:7.8 ± 0.70 vs 6.7 ± 0.71,P < 0.001).PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368(39.1%) human gastric cancer cases.PKM2 expression was not related with stage(P = 0.811),but strongly correlated with gastric cancer differentiation(P < 0.001).Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones.Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells;in contrast,signet-ring cell cancers showed only 17.7% PKM2-positive cells.Importantly,PKM2 expression was correlated with shorter overall survival(P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION:PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas.Its function and potential as a prognostic marker should be further verified in gastric cancer. 展开更多
关键词 Gastric cancer M2 isoform of pyruvate kinase Biomarker Signet ring cell carcinoma Prognosis
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Nanoscale metal organic frameworks inhibition of pyruvate kinase of M2 认领 引用 被引量：2
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作者 Xiangling Ren Xinyuan Huang +4 位作者 Qiong Wu Longfei Tan Changhui Fu Yi Chen Xianwei Meng 《Chinese Chemical Letters》 SCIE CAS CSCD 2021年第10期3087-3089,共3页
Tumor cells usually show abnormally high glycolysis rate to maintain the dynamic balance of energy.The growth of tumor cells can be affected by inhibiting the activity of pyruvate kinase(especially M2-type isozyme,PKM... Tumor cells usually show abnormally high glycolysis rate to maintain the dynamic balance of energy.The growth of tumor cells can be affected by inhibiting the activity of pyruvate kinase(especially M2-type isozyme,PKM2),the rate limiting enzyme of glycolysis.This is helpful to the treatment of tumor.Herein,metal organic frameworks(MOFs) were found to inhibit the activity of PKM2.Nanoscale ZIF-8 was synthesized by standing and ultrasonic method,respectively.The ZIF-8 has the performance of inhibiting PKM2.Further research showed that the inhibition ability was attributed to zinc ion in ZIF-8.Interestingly,the IC50 of ZIF-8 on PKM2 was one percent of that of zinc ion.This novel enzyme inhibitor is expected to be used in cancer therapy. 展开更多
关键词 Metal organic frameworks Pyruvate kinase Glycolysis Lactate dehydrogenase Inhibition
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Creatine Pyruvate Enhances Lipolysis and Protein Synthesis in Broiler Chicken 认领 引用 被引量：3
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作者 CHEN Juan MA Hai-tian +2 位作者 WANG Man KONG Yi-li ZOU Si-xiang 《Agricultural Sciences in China》 CSCD 2011年第12期1977-1985,共9页
To assess the effects ofcreatine pyruvate(Cr-Pyr)on lipid and protein metabolism in broiler chickens,a total of 4001-day-old male birds(Aconred)were randomly allocated to four groups,with each group replicating four t... To assess the effects ofcreatine pyruvate(Cr-Pyr)on lipid and protein metabolism in broiler chickens,a total of 4001-day-old male birds(Aconred)were randomly allocated to four groups,with each group replicating four times and each replicate involving 25 birds.The broilers were provided with a commercial diet supplemented with Cr-Pyr at 0,1,5,or 10%of the diet,respectively,for a period of 3 wk ad libitum(from 22 to 42 d).In the present study,body weight(BW)and average daily gain(ADG)of broilers decreased in 10%Cr-Pyr group(P〈0.01),whereas the relative leg and pectoral muscle weights were significantly higher than they were in the control group(P〈0.05).5 or 10%Cr-Pyr of diets decreased the abdominal fat rate(AFR,abdominal fat/live weight)of the broilers.The serum or hepatic triglyceride(TG)concentrations were significantly lower in the 5 and 10%groups(P〈0.01).In contrast,Cr-Pyr caused a marked increase in the serum nonesterified fatty acid(NEFA),high-density lipoprotein cholesterol(HDL-C)and creatine kinase(CK)concentrations(P〈0.01).Supplementation with Cr-Pyr(5 and 10%)in the diet also increased glucagons(GLU),insulin(INS)or leptin(LEP)contents(P〈0.01).The expression of hepatic peroxisomal proliferators-activated receptorα(PPAR-α)and carnitine palmitoyl transferase-I(CPT-I),muscle insulin-like growth factor I(IGF-I)were significantly elevated and myostatin mRNA level was reduced in the 5 and 10%groups(P〈0.05).It was found that supplementation with 5%Cr-Pyr improves both lipid and protein metabolism by regulating various metabolic parameters of broilers,while not adversely affects growth performance in broiler chickens. 展开更多
关键词 creatine pyruvate(Cr-Pyr) lipid metabolism protein metabolism liver muscle broiler chickens
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Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening:A meta-analysis 认领 引用 被引量：21
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作者 Carolin Tonus Markus Sellinger +1 位作者 Konrad Koss Gero Neupert 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第30期4004-4011,共8页
AIM:To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2(faecal M2-PK) test for colorectal cancer(CRC) screening based on the currently available studies.METHODS:A literatur... AIM:To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2(faecal M2-PK) test for colorectal cancer(CRC) screening based on the currently available studies.METHODS:A literature search in PubMed and Embase was conducted using the following search terms:fecal Tumor M2-PK,faecal Tumour M2-PK,fecal M2-PK,faecal M2-PK,fecal pyruvate kinase,faecal pyruvate kinase,pyruvate kinase stool and M2-PK stool.RESULTS:Stool samples from 704 patients with CRC and from 11 412 healthy subjects have been investigated for faecal M2-PK concentrations in seventeen independent studies.The mean faecal M2-PK sensitivity was 80.3%;the specificity was 95.2%.Four studies compared faecal M2-PK head-to-head with guaiacbased faecal occult blood test(gFOBT).Faecal M2PK demonstrated a sensitivity of 81.1%,whereas the gFOBT detected only 36.9% of the CRCs.Eight independent studies investigated the sensitivity of faecal M2-PK for adenoma(n = 554),with the following sensitivities:adenoma 1 cm:44%;adenoma of unspecified diameter:51%.In a direct comparison with gFOBT of adenoma > 1 cm in diameter,47% tested positive with the faecal M2-PK test,whereas the gFOBT detected only 27%.CONCLUSION:We recommend faecal M2-PK as a routine test for CRC screening.Faecal M2-PK closes a gap in clinical practice because it detects bleeding and nonbleeding tumors and adenoma with high sensitivity and specificity. 展开更多
关键词 Faecal pyruvate kinase isoenzyme type M2 Colorectal cancer screening Colorectal cancer Stool Faecal occult blood Adenoma Polyps
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Oxygen dependent pyruvate oxidase expression and production in Streptococcus sanguinis 认领 引用 被引量：2
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作者 Lan-yan Zheng Andreas Itzek +1 位作者 Zhi-yun Chen Jens Kreth 《International Journal of Oral Science》 SCIE CAS CSCD 2011年第2期82-89,共8页
The objective of this study was to characterize the oxygen dependent regulation of pyruvate oxidase （SpxB） gene expression and protein production in Streptococcus sanguinis （S. sanguinis）. SpxB is responsible for ... The objective of this study was to characterize the oxygen dependent regulation of pyruvate oxidase （SpxB） gene expression and protein production in Streptococcus sanguinis （S. sanguinis）. SpxB is responsible for the generation of growth-inhibiting amounts of hydrogen peroxide （H202） able to antagonize cariogenic Strepto- coccus mutans （S. mutans）. Furthermore, the ecological consequence of H202 production was investigated in its self-inhibiting ability towards the producing strain. Expression of spxB was determined with quantitative Real-Time RT-PCR and a fluorescent expression reporter strain. Protein abundance was investigated with FLAG epitope engineered in frame on the C-terminal end of SpxB. Self inhibition was tested with an antagonism plate assay. The expression and protein abundance decreased in cells grown under anaerobic conditions. S. sanguinis was resistant against its own produced H202, while cariogenic S. mutans was inhibited in its growth. The results suggest that S. sanguinis produces H202 as antimicrobial substance to inhibit susceptible niche competing species like S. mutans during initial biofilm formation, when oxygen availability allows for spxB expression and Spx production. 展开更多
关键词 Streptococcus sanguinis pyruvate oxidase oxygen dependent
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Biocatalytic Synthesis of Pyruvate from DL-lactate with Enzymes in Pseudomonas sp. 认领 引用 被引量：1
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作者 Jing Song GU Ping XU Yin Bo QU 《Chinese Chemical Letters》 SCIE CAS 2002年第12期1213-1216,共4页
A novel method of preparing pyruvate from DL-lactate catalyzed by enzymes from a bacterial strain of Pseudomonas sp. SM-6 was proposed. Catalytic processes of cell-free extract enzymes and immobilized enzymes were eva... A novel method of preparing pyruvate from DL-lactate catalyzed by enzymes from a bacterial strain of Pseudomonas sp. SM-6 was proposed. Catalytic processes of cell-free extract enzymes and immobilized enzymes were evaluated. The kinetic data were studied, too. 展开更多
关键词 Pyruvate DL-lactate biocatalyst enzyme Pseudomonas.
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MODIFICATION OF TRANSITION METAL CATIONS TO POLYMER-STABILIZED PLATINUM COLLOIDAL CLUSTERS IN ENANTIOSELECTIVE HYDROGENATION OF METHYL PYRUVATE 认领 引用 被引量：2
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作者 刘汉范 《Chinese Journal of Polymer Science》 SCIE EI CAS 2005年第4期393-399,共7页
Modification of transition metal cations to polymer-stabilized Pt colloidal clusters modified with cinchonidine was studied in enantioselective hydrogenation of methyl pyruvate.Compared to the enantiomeric excess(e.e.... Modification of transition metal cations to polymer-stabilized Pt colloidal clusters modified with cinchonidine was studied in enantioselective hydrogenation of methyl pyruvate.Compared to the enantiomeric excess(e.e.)value(71.4%) obtained without the presence of metal cations,obvious e.e.enhancement(up to 82.5%)was resulted from the addition of Zn2+ but with a certain decrease in activity.The reaction parameters in the presence of Zn2+ were also studied.It was found that the Pt colloidal catalysts in the presence of metal cations performed very differently from that in the absence of metal cations. 展开更多
关键词 Methyl pyruvate Colloidal platinum clusters Transition metal cations Enantioselective hydrogenation
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