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
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
目的本文拟采用体外实验,探讨脑细胞色素P450 2E1(cytochrome P450 2E1,CYP 2E1)在尼古丁致神经细胞氧化损伤中的可能作用。方法实验选用IMR-32人神经母细胞瘤细胞系,设置对照组,尼古丁小剂量组(0.1 n M)、中剂量组(1 n M)和大剂量组(10...目的本文拟采用体外实验,探讨脑细胞色素P450 2E1(cytochrome P450 2E1,CYP 2E1)在尼古丁致神经细胞氧化损伤中的可能作用。方法实验选用IMR-32人神经母细胞瘤细胞系,设置对照组,尼古丁小剂量组(0.1 n M)、中剂量组(1 n M)和大剂量组(10 n M),并选用中剂量尼古丁加入不同剂量CYP2E1特异性抑制剂二丙烯基硫醚(diallyl sulfide,DAS)(0.025、0.05、0.075 n M)。尼古丁或尼古丁与二丙烯基硫醚处理细胞48 h。取处理后细胞,分别检测乳酸脱氢酶(lactate dehydrogenase,LDH)、超氧化物歧化酶(superoxide dismutase,SOD)、活性氧(reactive oxygen species,ROS)、CYP2E1mRNA和蛋白水平的变化,并对CYP2E1蛋白表达水平与LDH活力、SOD活力、ROS含量进行相关性分析。结果与对照组相比,经低、中、高剂量尼古丁处理后,IMR-32细胞增殖受抑制,抑制率分别为39%、47%、52%(均P<0.05);细胞受到损伤,培养基LDH活力分别升高14%、50%、70%(均P<0.05);SOD活力下降至对照组的76%、58%、44%(均P<0.05);细胞CYP2E1蛋白表达水平显著升高至2.19、2.65及2.76倍(均P<0.05),未见CYP2E1 mRNA水平改变;ROS生成量升高48%、65%、136%(均P<0.05)。与尼古丁(1 nm)组相比,加入低、中、高剂量抑制剂后,SOD活力升高24%、47%、52%(均P<0.05);ROS含量下降至77.8%、57.8%、44.3%(均P<0.05)。相关性分析显示,CYP2E1含量与LDH活力呈正相关,与SOD活力呈负相关,相关系数分别为0.740和-0.584,与ROS含量呈正相关,相关系数为0.695(均P<0.01)。结论尼古丁处理可抑制IMR-32细胞增殖,诱导脑CYP2E1表达,明显诱导ROS生成,致神经细胞损伤。展开更多
Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic ac...Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.展开更多
目的考察CYP2E1*5B(G-1293C)和CYP2E1*6(T7632A)基因多态性与急性淋巴细胞白血病(ALL)易感性及其与甲氨蝶呤(MTX)血清浓度的相关性。方法收集283名健康对照者和91例ALL患儿的外周血,提取DNA。用聚合酶链反应-限制性片断长度多态性法(PCR...目的考察CYP2E1*5B(G-1293C)和CYP2E1*6(T7632A)基因多态性与急性淋巴细胞白血病(ALL)易感性及其与甲氨蝶呤(MTX)血清浓度的相关性。方法收集283名健康对照者和91例ALL患儿的外周血,提取DNA。用聚合酶链反应-限制性片断长度多态性法(PCR-RFLP)检测CYP2E1*5B和CYP2E1*6基因型,用荧光偏振免疫分析法(FPIA)测定24,42 h MTX血清浓度。结果 ALL患儿的C(*5B)等位基因频率(24.73%)显著高于健康对照人群(17.31%)(P<0.05);C等位基因频率的优势比(OR)为1.57,C等位基因显著增加ALL的发病风险(P<0.05)。ALL患儿与健康对照人群的CYP2E1*6的基因型与等位基因分布频率相近,CYP2E1*6与ALL的发病风险无显著相关关系。CYP2E1*5B和CYP2E1*6各基因型组ALL患儿的24,42 h MTX浓度与剂量比值(C/D ratio)没有显著差异。结论 CYP2E1*5B可显著增加ALL的发病风险,但CYP2E1*6与ALL的发生无关;C等位基因是ALL的易感等位基因,两者的基因多态性与MTX血清浓度无显著相关关系。展开更多
基金Supported by NIH/NIAAA Grants No. AA017425Supported by NIH/NIAAA Grants No. AA018790
文摘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.
基金supported by the Chunhui Plan from Ministry of Eduction of ChinaFund for Academy Leaders and Innovative Team from Inner Mongolian Autonomous Region of china
文摘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.
基金financially supported by National Natural Science Foundation of China(81700524)Natural Science Foundation of Fujian Province(2022J01866)from Fujian Provincial Department of Science and Technology+1 种基金Key Project of Fujian University of Traditional Chinese Medicine(X2021019)Collaborative Innovation and Platform Establishment Project of Department of Science and Technology of Guangdong Province(2019A050520003)。
文摘Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.
文摘目的考察CYP2E1*5B(G-1293C)和CYP2E1*6(T7632A)基因多态性与急性淋巴细胞白血病(ALL)易感性及其与甲氨蝶呤(MTX)血清浓度的相关性。方法收集283名健康对照者和91例ALL患儿的外周血,提取DNA。用聚合酶链反应-限制性片断长度多态性法(PCR-RFLP)检测CYP2E1*5B和CYP2E1*6基因型,用荧光偏振免疫分析法(FPIA)测定24,42 h MTX血清浓度。结果 ALL患儿的C(*5B)等位基因频率(24.73%)显著高于健康对照人群(17.31%)(P<0.05);C等位基因频率的优势比(OR)为1.57,C等位基因显著增加ALL的发病风险(P<0.05)。ALL患儿与健康对照人群的CYP2E1*6的基因型与等位基因分布频率相近,CYP2E1*6与ALL的发病风险无显著相关关系。CYP2E1*5B和CYP2E1*6各基因型组ALL患儿的24,42 h MTX浓度与剂量比值(C/D ratio)没有显著差异。结论 CYP2E1*5B可显著增加ALL的发病风险,但CYP2E1*6与ALL的发生无关;C等位基因是ALL的易感等位基因,两者的基因多态性与MTX血清浓度无显著相关关系。
