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Interplay of Cytochrome P450 genes and flavonoid pathways in enhancing plant defense against heavy metal toxicity 认领 引用
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作者 Yuanpeng Fang Zehui Wang +2 位作者 Salah F.Abou-Elwafa Maha Aljabri Xin Xie 《Horticultural Plant Journal》 SCIE CAS CSCD 2026年第3期653-669,共17页
Toxic heavy metal and metalloid(THMM)contamination poses a major global challenge,threatening human health and sustainable agriculture.The crucial role of the Cytochrome P450(CYP)gene family in plant tolerance to THMM... Toxic heavy metal and metalloid(THMM)contamination poses a major global challenge,threatening human health and sustainable agriculture.The crucial role of the Cytochrome P450(CYP)gene family in plant tolerance to THMMs has been recently highlighted,but there is still a lack of comprehensive understanding,especially in relation to metabolites.This study delved into the identification of CYP genes that are linked to the tolerance mechanisms of plants in response to heavy metal stress.The findings highlight the significant metabolic pathways that contribute to this resilience,using rice and Arabidopsis as exemplars.THMM exposure changed CYP gene expression in plants,and THMM antidotes mitigated its downregulation and that of flavonoid biosynthesis genes.CYP genes involved in THMM responses were predominantly enriched in the pathways associated with flavonoid synthesis,indicating functional adaptations to distinct stresses.Notably,anthocyanin(Ant)accumulation,a type of flavonoid,affected the uptake of various heavy metals in Brassica rapa,with flavonoid biosynthesis-associated genes correlating with Cd or As tolerance and Ant content.These findings highlight the critical importance of flavonoid metabolism and the intricate network of biosynthesis genes in bolstering plant resilience against heavy metal stress.This enhanced understanding paves the way for significant advancements in phytoremediation technologies,offering innovative solutions for soil and water decontamination. 展开更多
关键词 Heavy metals Cytochrome P450 Flavonoid biosynthesis Anthocyanin Plant tolerance
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Two genes of cytochrome P450 regulate plant height via brassinosteroid biosynthesis in Brassica napus 认领 引用 被引量：2
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作者 Qianqian Zheng Xinhua Wang +11 位作者 Zhenzhen Wang Yi Zhang Hao Wang Kangxi Du Shaohong Fu Wanzhuo Gong Hua Yuan Weilan Chen Bin Tu Jin Yang Yun Li Ting Li 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2026年第8期3153-3168,共16页
Rapeseed(Brassica napus)is one of the most important oil crops worldwide and provides a major source of edible vegetable oil.Currently,manipulating plant height with branching effectively balances biomass and yields.H... Rapeseed(Brassica napus)is one of the most important oil crops worldwide and provides a major source of edible vegetable oil.Currently,manipulating plant height with branching effectively balances biomass and yields.However,the genetic mechanisms to control plant height remain largely unknown in rapeseed.To address this gap,we isolated an extremely dwarf mutant(dm1)from ethyl-methanesulfonate(EMS)mutagenesis and revealed that the dwarfism results from a significant reduction in cell length.Bulk segregant analysis(BSA)identified BnaA10.CYP90A1 and BnaC09.CYP90A1 as the causative genes of dm1.Both genes encoded the proteins homologous to the Arabidopsis cytochrome P450 AtCPD/AtCYP90A1,which is crucial for brassinosteroid(BR)biosynthesis.In this regard,we demonstrated reduced levels of bioactive BRs,castasterone(CS),and its precursor 6-deoxoCS in dm1,resulting in down-regulation of various genes involved in cell expansion.The reduced BR levels also caused negative feedback,promoting the expression of BR biosynthetic genes in dm1.Furthermore,we proved that the single mutation of BnaA10.CYP90A1 gene conferred semi-dwarfism,potentially beneficial for producing an ideal type of plant to improve cultivars with a balance of yield and machinery harvest through genetic modifications.Collectively,these findings highlighted the critical role of BnaCYP90A1s in BR biosynthesis and validated their influence on plant height regulation in rapeseed. 展开更多
关键词 plant height BR biosynthesis cytochrome P450 Brassica napus
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Mining substrate-promiscuity cytochrome P450s from Euphorbia fischeriana for heterologous bioproduction of diverse labdane-related diterpenoids 认领 引用
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作者 Ke Gao Lin Zhao +4 位作者 Lei Wang Rui Zhang Jianxun Zhu Pengcheng Lin Jiachen Zi 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第1期389-393,共5页
Many labdane-related diterpenoids(LRDs)exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrome... Many labdane-related diterpenoids(LRDs)exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrome P450s(CYPs).The medicinal plant Euphorbia fischeriana Steud.is rich in LRDs with distinct scaffolds.Herein,we characterized three cytochrome P450s involved in LRD biosynthesis from this plant.Notably,CYP71D450 and CYP701A148 are two substrate-promiscuity CYPs.The former is the first example of CYPs which can oxidize C-3 of ent-atisane skeleton and ent-isopimara-7(8),15-diene,and the latter is the first example of CYPs which can oxidize C-19 of ent-abietane and ent-pimarane skeletons.This study expands the toolkit for bioproduction of diverse LRDs. 展开更多
关键词 Labdane-related diterpenoids Biosynthesis Cytochrome P450 Bioproduction Euphorbia fischeriana
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Cyt02 encodes cytochrome P450 monooxygenase,increasing rice(Oryza sativa L.)resistance to sheath blight 认领 引用 被引量：1
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作者 Tengda Zheng Xiaolin Wang +9 位作者 Yuewen He Deqiang Li Andrews Danso Ofori Xing Xiang Abdul Ghani Kandhro Xiaoqun Yi Fu Huang Jianqing Zhu Ping Li Aiping Zheng 《The Crop Journal》 SCIE CAS CSCD 2025年第1期92-103,共12页
Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are... Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are not yet fully understood.Cytochrome P450 monooxygenases(CYP450s)serve biosynthesis and metabolic detoxification functions in plants,but there is limited information about their role in the response induced by RSB.This study demonstrated that CYT02 belongs to the CYP73A100 subfamily and is a typical member of the CYP450s.Overexpression(OE)in rice of the cytochrome P450 monooxygenase cyt02 conferred increased resistance to RSB and increased vegetative tillering.Cyt02 may increase RSB resistance by regulating plant hormone synthesis,regulate reactive oxygen species(ROS)by coordinating the activity of antioxidant enzymes,and initiate phytoalexin synthesis in response to fungal infection.These research findings have laid a foundation for a deeper understanding of the function of cyt02 and offered a potential target gene for breeding rice varieties resistant to sheath blight. 展开更多
关键词 Rice Sheath blight Cytochrome P450 monooxygenase Metabolomics analysis Functional analysis
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Involvement of the cytochrome P450 genes CYP6DW3 and CYP4C64 in afidopyropen resistance in Bemisia tabaci Mediterranean(Q biotype) 认领 引用 被引量：1
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作者 Lijun Ma Juan Tang +4 位作者 Qinghe Zhang Bingli Gao Cheng Qu Ran Wang Chen Luo 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2025年第5期1905-1915,共11页
The tobacco whitefly,Bemisia tabaci,is a notorious pest affecting various crops globally,and it exhibits high levels of resistance to various insecticides.Afidopyropen is a recently commercialized pyropene insecticide... The tobacco whitefly,Bemisia tabaci,is a notorious pest affecting various crops globally,and it exhibits high levels of resistance to various insecticides.Afidopyropen is a recently commercialized pyropene insecticide for B.tabaci control with high selectivity and a novel mode of action.We previously identified a high level of afidopyropen resistance in a field-collected population after selection in the lab,and named it the HD-Afi strain.In the present study,minimal cross-resistance in the HD-Afi strain was found between afidopyropen and other common chemical agents.However,the P450 enzyme activity in HD-Afi was 2.18 times the level in susceptible strain HD-S.Expression analysis revealed that two of 12 candidate P450 genes,namely CYP6DW3 and CYP4C64,were significantly up-regulated in HD-Afi.Silencing CYP6DW3 and CYP4C64 by RNA interference(RNAi)substantially increased the susceptibility of whitefly adults,confirming their involvement in afidopyropen resistance.Homology modeling and molecular docking analyses demonstrated stable binding of afidopyropen to CYP6DW3 and CYP4C64,with binding free energies of–6.87 and–6.11 kcal mol-1,respectively.The findings of this study suggest that the induction of CYP6DW3 and CYP4C64 facilitates afidopyropen detoxification,contributing to the development of resistance in B.tabaci. 展开更多
关键词 Bemisia tabaci afidopyropen insecticide detoxification cytochrome P450 monooxygenase
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Shenzhuo formulation ameliorates diabetic nephropathy by regulating cytochrome P450-mediated arachidonic acid metabolism 认领 引用 被引量：1
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作者 Zhong-Yong Zhang Yu-Ming Wang +8 位作者 Ning Wang Yuan-Song Wang Hui Zhang Duo Wang Li-Xin Wang Huan-Tian Cui Wei-Bo Wen Shu-Quan Lv Yong-Jun Cao 《World Journal of Diabetes》 SCIE 2025年第5期331-345,共15页
BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effec... BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effective treatment options remain limited.AIM To evaluate the therapeutic impact of Shenzhuo formulation(SZF)on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.METHODS We established a DN mouse model through a high-fat diet combined with streptozotocin(STZ)injection,followed by SZF treatment.We analyzed SZF’s effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques.Additionally,based on transcriptomic and non-targeted metabolomic findings,we further assessed SZF’s influence on the expression of factors related to the cytochrome P450(CYP450)-mediated arachidonic acid(AA)metabolism pathway,as well as its effects on inflammation and oxidative stress.RESULTS SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice.Pathological analysis revealed that SZF treatment improved renal tissue damage,reduced fibrosis,and diminished glycogen deposition.Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes,including Cyp2j13,Cyp2b9,Pla2 g2e/Cyp4a12a,Cyp4a32,Cyp2e1,and Cyp4a14.Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway,including 5,6-EET,14,15-EET,phosphatidylcholine,and 20-HETE.Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue,as well as CYP2J and CYP2B proteins.Additionally,SZF significantly reduced the expression of inflammatory factors in renal tissue,enhanced antioxidant enzyme activity,and alleviated oxidative stress.CONCLUSION SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism,leading to improved renal function and improved pathological state in DN mice. 展开更多
关键词 Diabetic nephropathy Shenzhuo formulation Transcriptomic Metabolomic Cytochrome P450 Arachidonic acid metabolic Inflammatory Oxidative stress
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Elucidating the Substrate Specificity of Cytochrome P450 Enzymes:Insights into N-and S-Containing Small-Molecule Metabolism 认领 引用
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作者 Chaohua Yan Guilin Wei +4 位作者 Zhuoan Jin Xiaodong Li Liuyi Yang Liwei Zou Ling Yang 《Engineering》 SCIE EI CSCD 2025年第11期229-250,共22页
Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of ... Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of reactions,including metabolic reactions that occur at nitrogen(N)and sulfur(S)sites of small molecules.In this review,we conducted a comprehensive statistical analysis of 294 P450s-mediated small-molecule substrates,among which more than 47%substrates contained N and S.The purpose of the analysis is to elucidate the broad-spectrum cross-reactivity and specificity between these substrates and various CYP isoforms across five reaction types.Our findings reveal that substrates with molecular weights greater than 500 Da or less than 200 Da are predominantly governed by the dominant effect of the CYP isoform’s active sites.In contrast,small-to medium-sized molecules with molecular weights ranging from 200 to 400 Da exhibit a stronger dependence on the types of heteroatoms they contain,with the size of the enzyme’s catalytic site(cavity)playing a negligible role in determining substrate specificity.This review starts from the metabolic mechanisms of P450s-mediated N-and S-containing compounds,and systematically analyzes the structural characteristics of substrates involved in N-dealkylation,N-oxidation,and S-oxidation,as well as their metabolic interactions with P450s.These analyses provide a new perspective for improving the existing understanding of the relationship between the P450s substrate specificity and substrate structural characteristics,and offer a valuable perspective for enhancing drug design and predicting metabolic stability based on the P450s-catalyzed reaction framework. 展开更多
关键词 Drug metabolism Cytochrome P450 enzymes Active sites/catalytic sites Substrate specificity N-and S-containing substrates
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Cardioprotection of Shenfu preparata on cardiac myocytes through cytochrome P450 2J3 认领 引用 被引量：18
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作者 Yong Xiao Zeng-chun Ma +5 位作者 Yu-guang Wang Hong-ling Tan Xiang-ling Tang Qian-de Liang Cheng-rong Xiao Yue Gao 《Journal of Integrative Medicine》 CAS CSCD 2013年第5期327-336,共10页
To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and S... To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3. 展开更多
关键词 Shenfu decoction cardiotonic agents cytochrome P450 2J3 plant extracts in vitro
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Bacterial cytochrome P450‑catalyzed regioand stereoselective steroid hydroxylation enabled by directed evolution and rational design 认领 引用 被引量：10
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作者 Xiaodong Zhang Yaqin Peng +4 位作者 Jing Zhao Qian Li Xiaojuan Yu Carlos G.Acevedo‑Rocha Aitao Li 《Bioresources and Bioprocessing》 SCIE EI 2020年第1期837-854,共18页
Steroids are the most widely marketed products by the pharmaceutical industry after antibiotics.Steroid hydroxylation is one of the most important functionalizations because their derivatives enable a higher biologica... Steroids are the most widely marketed products by the pharmaceutical industry after antibiotics.Steroid hydroxylation is one of the most important functionalizations because their derivatives enable a higher biological activity compared to their less polar non-hydroxylated analogs.Bacterial cytochrome P450s constitute promising biocatalysts for steroid hydroxylation due to their high expression level in common workhorses like Escherichia coli.However,they often suffer from wrong or insufficient regio-and/or stereoselectivity,low activity,narrow substrate range as well as insufficient thermostability,which hampers their industrial application.Fortunately,these problems can be generally solved by protein engineering based on directed evolution and rational design.In this work,an overview of recent developments on the engineering of bacterial cytochrome P450s for steroid hydroxylation is presented. 展开更多
关键词 Biocatalysis Cytochrome P450 Steroid hydroxylation Regioselectivity Stereoselectivity Directed evolution Rational design
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The cytochrome P450 superfamily: Key players in plant development and defense 认领 引用 被引量：39
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作者 XU Jun WANG Xin-yu GUO Wang-zhen 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2015年第9期1673-1686,共14页
The cytochrome P450 （CYP） superfamily is the largest enzymatic protein family in plants, and it also widely exists in mammals, fungi, bacteria, insects and so on. Members of this superfamily are involved in multiple... The cytochrome P450 （CYP） superfamily is the largest enzymatic protein family in plants, and it also widely exists in mammals, fungi, bacteria, insects and so on. Members of this superfamily are involved in multiple metabolic pathways with distinct and complex functions, playing important roles in a vast array of reactions. As a result, numerous secondary metabolites are synthesized that function as growth and developmental signals or protect plants from various biotic and abiotic stresses. Here, we summarize the characterization of CYPs, as well as their phylogenetic classification. We also focus on recent advances in elucidating the roles of CYPs in mediating plant growth and development as well as biotic and abiotic stresses responses, providing insights into their potential utilization in plant breeding. 展开更多
关键词 cytochrome P450 phylogenetic classification plant growth and development biotic and abiotic stress
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Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma 认领 引用 被引量：7
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作者 I Bergheim E Wolfgarten +3 位作者 E Bollschweiler AH Hlscher C Bode A Parlesak 《World Journal of Gastroenterology》 SCIE CAS 2007年第7期997-1002,共6页
AIM： To investigate the role of cytochrome P450 （CYP） in the carcinogenesis of squamous-cell carcinoma （SCC） in human esophagus by determining expression patterns and protein levels of representative CYPs in esop... AIM： To investigate the role of cytochrome P450 （CYP） in the carcinogenesis of squamous-cell carcinoma （SCC） in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls. METHODS： mRNA expression of CYP2E1, CYP2C, CYP3A4, and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC （/7 = 21） and in controls （n = 10）. Protein levels of CYP2E1, CYP2CS, CYP3A4, and CYP3A5 were measured by Western blot. RESULTS： Within the group of SCC patients, mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue （-39% and -74%, respectively, P 〈 0.05） than in normal tissue. Similar results were found in CYP3A4 protein levels. Between groups, CYP3A4, CYP3A5, and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients （4.8-, 2.9-, and 1.9-fold elevation, P 〈 0.05） than in controls. In contrast, CYP2E1 protein levels were significantly higher in controls than in SCC patients （＋46%, P 〈 0.05）. CONCLUSION： Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue （e.g. CYP2CB, CYP3A4, CYP3A5, and CYP2E1） between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus. 展开更多
关键词 Squamous-cell carcinoma Cytochrome P450 Western blot RT-PCR Human
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Tunnel engineering for modulating the substrate preference in cytochrome P450BsβHI 认领 引用 被引量：4
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作者 Shuaiqi Meng Ruipeng An +8 位作者 Zhongyu Li Ulrich Schwaneberg Yu Ji Mehdi D.Davari Fang Wang Meng Wang Meng Qin Kaili Nie Luo Liu 《Bioresources and Bioprocessing》 SCIE EI 2021年第1期1556-1565,共10页
An active site is normally located inside enzymes,hence substrates should go through a tunnel to access the active site.Tunnel engineering is a powerful strategy for refining the catalytic properties of enzymes.Here,P... An active site is normally located inside enzymes,hence substrates should go through a tunnel to access the active site.Tunnel engineering is a powerful strategy for refining the catalytic properties of enzymes.Here,P450BsβHI (Q85H/V170I) derived from hydroxylase P450Bsβ from Bacillus subtilis was chosen as the study model,which is reported as a potential decarboxylase.However,this enzyme showed low decarboxylase activity towards long-chain fatty acids.Here,a tunnel engineering campaign was performed for modulating the substrate preference and improving the decarboxylation activity of P450BsβHI.The finally obtained BsβHI-F79A variant had a 15.2-fold improved conversion for palmitic acid;BsβHI-F173V variant had a 3.9-fold improved conversion for pentadecanoic acid.The study demonstrates how the substrate preference can be modulated by tunnel engineering strategy. 展开更多
关键词 Tunnel engineering Substrate preference Cytochrome P450BsβHI α-Alkene biosynthesis Rational design
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Long-term modifications of blood pressure in normotensive and spontane-ously hypertensive rats by gene delivery of rAAV-mediated cytochrome P450 arachidonic acid hydroxylase 认领 引用 被引量：3
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作者 Fan ZHANG Chun Lian CHEN +4 位作者 Jia Qing QIAN Jiang Tao YAN Katherine CIANFLONE Xiao XIAO Dao Wen WANG 《Cell Research》 SCIE CAS 2005年第9期717-724,共8页
Arachidonic acid cytochrome P-450 （CYP） hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids （20-HETE）, a biologicall... Arachidonic acid cytochrome P-450 （CYP） hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids （20-HETE）, a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adenoassociated viral vector （rAAV） to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into Sprague-Dawley （SD） rats and spontaneously hypertensive rats （SHR）, respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hyperténsion. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV.4A 1-treated SD rats and decreased by 13.7±2.2 mm Hg in rAAV.anti4A l-treated SHR rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24 weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mRNA and protein levels. In anti-4Al-treated SHR, CYP4A mRNA in various tissues was probed, especially in kidneys, but 4A l protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxylases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension. rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hypertension by blocking expression of CYP 4A in kidneys. 展开更多
关键词 Arachidonic acid cytochrome P450 4A1 hypertension recombinant adeno-associated virus 20-Hydroxyeicosatetraenoic acids spontaneously hypertensive rats
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Genomic and transcriptomic insights into cytochrome P450 monooxygenase genes involved in nicosulfuron tolerance in maize(Zea mays L.) 认领 引用 被引量：2
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作者 LIU Xiao-min XU Xian +4 位作者 LI Bing-hua YAO Xiao-xia ZHANG Huan-huan WANG Gui-qi HAN Yu-jun 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2018年第8期1790-1799,共10页
Postemergence application of nicosulfuron for weed control in maize fields can cause great damage to certain maize inbred lines and hybrids. Two maize genotypes, tolerant inbred(HBR) and sensitive inbred(HBS), were fo... Postemergence application of nicosulfuron for weed control in maize fields can cause great damage to certain maize inbred lines and hybrids. Two maize genotypes, tolerant inbred(HBR) and sensitive inbred(HBS), were found to significantly differ in their phenotypic responses to nicosulfuron, with the EC50(50% effective concentration) values differed statistically(763.6 and 5.9 g a.i. ha–1, respectively). Pre-treatment with malathion, a known cytochrome P450 inhibitor, increased nicosulfuron injury in both HBR and HBS. Our results support the hypothesis that nicosulfuron selectivity in maize is associated with cytochrome P450 metabolism. Further analysis of the maize genome resulted in the identification of 314 full length cytochrome P450 monooxygenase(CYP) genes. These genes were classified into 2 types, 10 clans and 44 families. The CYP71 clan was represented by all A-type genes(168) belonging to 17 families. Nine clans possessed 27 families containing 146 non-A-type genes. The consensus sequences of the heme-binding regions of A-type and non-A-type CYP proteins are ‘PFGXGRRXCPG’ and ‘FXXGPRXCXG’, respectively. Illumina transcriptome sequence results showed that there were 53 differentially expressed CYP genes on the basis of high variation in expression between HBS and HBR, nicosulfuron-treated and untreated samples. These genes may contribute to nicosulfuron tolerance in maize. A hierarchical clustering analysis obtained four main clusters named C1 to C4 in which 4, 15, 21, and 13 CYP genes were found in each respective cluster. The expression patterns of some CYP genes were confirmed by RT-q PCR analysis. The research will improve our understanding of the function of maize cytochrome P450 in herbicide metabolism. 展开更多
关键词 cytochrome P450 Zea mays L. malathion nicosulfuron herbicide metabolism
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Cytochrome P450 2E1 RsaI/PstI and DraI Polymorphisms Are Risk Factors for Lung Cancer in Mongolian and Han Population in Inner Mongolia 认领 引用 被引量：3
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作者 Xiu-lan Su Ba Bin +1 位作者 Hong-wei Cui Mei-rong Ran 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2011年第2期107-111,共5页
Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E... Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results： The risk of lung cancer was increased in individuals with CYP2E1 （cl/cl） and CYP2E1 （DD） with OR values of 2.431 （95%CI=1.082-5.460） and 2.778 （95%CI=1.358-5.683） respectively （P0.05）. When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 （cl/c2＋c2/c2 and DD＋CC） with OR values of 0.233 （95%CI=0.088-0.615, P0.05）. In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 （c1/c1） and CYP2E1 （DD） than in the individuals with c2 and C allele （P0.05, OR=2.643 and 4.308 respectively）. There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion： CYP2E1 （c1/c1） and CYP2E1 （DD） are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 （c2﹢C） co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 （c1/c1） and CYP2E1 （DD） on the occurrence of lung cancer. 展开更多
关键词 Cytochrome p450 2E1 Gene polymorphism Lung cancer Susceptivity
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Creation of cytochrome P450 catalysis depending on a non-natural cofactor for fatty acid hydroxylation 认领 引用 被引量：2
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作者 Qing Li Xiaojia Guo +4 位作者 Xueying Wang Junting Wang Li Wan Haizhao Xue Zongbao K.Zhao 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2023年第4期31-36,共6页
Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-p... Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M-1s-1for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system. 展开更多
关键词 Biocatalysis Cytochrome P450 Directed evolution Fatty acid hydroxylation Non-natural cofactor Synthetic biology
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Inhibitive Effect of Cremophor RH40 or Tween 80-based Self-microemulsiflying Drug Delivery System on Cytochrome P450 3A Enzymes in Murine Hepatocytes 认领 引用 被引量：7
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作者 饶子超 斯陆勤 +3 位作者 关延彬 潘洪平 裘军 李高 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2010年第5期562-568,共7页
This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazola... This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates. 展开更多
关键词 midazolam Cremophor RH40 Tween 80 cytochrome P450 3A self-microemulsifying drug delivery systems
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Identification of a cytochrome P450 from Tripterygium hypoglaucum(Levl.)Hutch that catalyzes polpunonic acid formation in celastrol biosynthesis 认领 引用 被引量：2
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作者 CHEN Xiao-Chao LU Yun +5 位作者 LIU Yuan ZHOU Jia-Wei ZHANG Yi-Feng GAO Hai-Yun LIDan GAO Wei 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2022年第9期691-700,共10页
Tripterygium hypoglaucum(Levl.)Hutch,a traditional Chinese medicinal herb with a long history of use,is widely distributed in China.One of its main active components,celastrol,has great potential to be developed into ... Tripterygium hypoglaucum(Levl.)Hutch,a traditional Chinese medicinal herb with a long history of use,is widely distributed in China.One of its main active components,celastrol,has great potential to be developed into anti-cancer and anti-obesity drugs.Although it exhibits strong pharmacological activities,there is a lack of sustainable sources of celastrol and its derivatives,making it crucial to develop novel sources of these drugs through synthetic biology.The key step in the biosynthesis of celastrol is considered to be the cyclization of 2,3-oxidosqualene into friedelin under the catalysis of 2,3-oxidosqualene cyclases.Friedelin was speculated to be oxidized into celastrol by cytochrome P450 oxidases(CYP450s).Here,we reported a cytochrome P450 ThCYP712K1 from Tripterygium hypoglaucum(Levl.)Hutch that catalyzed the oxidation of friedelin into polpuonic acid when heterologously expressed in yeast.Through substrate supplementation and in vitro enzyme analysis,ThCYP712K1 was further proven to catalyze the oxidation of friedelin at the C-29 position to produce polpunonic acid,which is considered a vital step in the biosynthesis of celastrol,and will lay a foundation for further analysis of its biosynthetic pathway. 展开更多
关键词 Tripterygium hypoglaucum Cytochrome P450 Polpunonic acid Celastrol Biosynthesis
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Down-regulated Expression of Cytochrome P450 Related Genes Involved in Hepatocellular Carcinoma 认领 引用 被引量：6
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作者 刘秀峰 施瑞华 +4 位作者 王学浩 张国新 朱宏 郜恒骏 秦叔逵 《The Chinese-German Journal of Clinical Oncology》 2006年第3期159-164,共6页
Objective： To analyze the differentially expressed genes （DEGs） among hepatocellular carcinoma （HCC）, para-cancerous tissue （PCT） and normal liver tissue （NLT） by using hgilent microarray and explore the targ... Objective： To analyze the differentially expressed genes （DEGs） among hepatocellular carcinoma （HCC）, para-cancerous tissue （PCT） and normal liver tissue （NLT） by using hgilent microarray and explore the target genes related to the development and progression of HCC. Methods： Total RNA of matched HCC, PCT and NLT of HCC patients was isolated using one step Trizol method and qualified using Lab-onchip method, cRNAs were synthesized, fluoresce labeled and purified after total RNAs purified. The RNAs of HCC and NLT, HCC and PCT were hybridized to Agilent microarray （21 074 probes） respectively. The fluorescence intensities were detected by Agilent scanner and quantified by Feature Extraction software. The DEGs which both differentially expressed in HCC vs NLT and HCC vs PCT were selected as candidate genes and confirmed by SYBR Green I stained real time RT-PCR. Results： （1） The total RNAs, reverse transcription products and fluoresce labeled cRNAs were of high quality; （2） There were 420 up-regulated genes and 552 down-regulated genes in 2-fold DEGs, including 23 genes related to cytochrome P450; （3） CYP2C8 was selected as a candidate gene of 10-fold down-regulated genes. The results of real time RTPCR, using β-actin as an internal control, revealed that the 2^-ΔCt values of CYP2C8 in HCC, PCT and NLT were 0.009383, 0.316812 and 0.607182, respectively. Conclusion： （1） The high throughput and effective Agilent oligomicroarray can screen novel therapy target genes by analyzing the DGEs in development and progression of HCC; （2） The development and progression of HCC is a complicated process involving multigenes and multiprocedures; （3） Down-regulated expression of cytochrome P450 related genes maybe involved in the development and progression of HCC due to the increased activity of certain carcinogens and maybe the exact mechanism need further study. 展开更多
关键词 hepatocellular carcinoma oligomicroarray cytochrome P450
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Hepatoprotective effects of S-adenosyl-L-methionine against alcohol-and cytochrome P450 2E1-induced liver injury 认领 引用 被引量：28
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作者 Arthur I Cederbaum 《World Journal of Gastroenterology》 SCIE CAS 2010年第11期1366-1376,共11页
S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death... S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection. 展开更多
关键词 Cytochrome P450 2E1 S-adenosyl-L-methionine Ethanol Toxic hepatitis Oxidative stress
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