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
Background Cytochrome P450 2E1 （CYP2E1） has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined wheth...Background Cytochrome P450 2E1 （CYP2E1） has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined whether CYP2E1 Rsal and Dral polymorphism are associated with susceptibility to esophageal squamous cell carcinoma and the correlation between the genotypes and expression levels of CYP2E1 mRNA.Methods Seventy-seven patients with newly diagnosed, untreated esophageal squamous cell carcinoma and 79 healthy controls matched in age, gender and residence were recruited for the control study. An Rsal polymorphism in the 5＇-flanking region and a Dral polymorphism in the sixth intron of the CYP2E1 gene, which could possibly affect its transcription, were determined in this study by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and mRNA level of CYP2E1 was measured by quantitative real-time reverse transcription PCR.Results No significant association of Rsal or Dral polymorphism of CYP2E1 with susceptibility of esophageal squamous cell carcinoma were demonstrated （OR=1.67, 95%CI： 0.89-3.15, P=0.11; OR=1.11, 95%CI： 0.59-2.09, P=0.74, respectively）. With SHEsis software, no linkage disequilibrium was detected between Rsal and Dral polymorphism （D＇=0.528, r^2=0.27）. When combined Rsal polymorphism with Dral polymorphism, the association between that carrying c2 allele and DD genotype and the risk for esophageal squamous cell carcinoma were found （OR=5.77, 95%CI： 1.65-20.22）. Compared with the normal controls, the mRNA levels with Rsal polymorphism, Dral polymorphism, or any combined genotypes in cases showed no statistical difference.Conclusions This study suggests that carrying c2 allele and DD genotype conferreded an elevated risk for esophageal squamous cell carcinoma. There was no significant statistical relationship between the genotypes c1/c2, D/C, or the combined allele and mRNA expression.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the National Nature Science Foundation of China(No.30671732 and No.30571540)the Preventive Medicine Foundation of Jiangsu Province(No.Y2006007)the National Science Development Foundation of Southeast University(No.XJ0525212)
文摘Background Cytochrome P450 2E1 （CYP2E1） has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined whether CYP2E1 Rsal and Dral polymorphism are associated with susceptibility to esophageal squamous cell carcinoma and the correlation between the genotypes and expression levels of CYP2E1 mRNA.Methods Seventy-seven patients with newly diagnosed, untreated esophageal squamous cell carcinoma and 79 healthy controls matched in age, gender and residence were recruited for the control study. An Rsal polymorphism in the 5＇-flanking region and a Dral polymorphism in the sixth intron of the CYP2E1 gene, which could possibly affect its transcription, were determined in this study by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and mRNA level of CYP2E1 was measured by quantitative real-time reverse transcription PCR.Results No significant association of Rsal or Dral polymorphism of CYP2E1 with susceptibility of esophageal squamous cell carcinoma were demonstrated （OR=1.67, 95%CI： 0.89-3.15, P=0.11; OR=1.11, 95%CI： 0.59-2.09, P=0.74, respectively）. With SHEsis software, no linkage disequilibrium was detected between Rsal and Dral polymorphism （D＇=0.528, r^2=0.27）. When combined Rsal polymorphism with Dral polymorphism, the association between that carrying c2 allele and DD genotype and the risk for esophageal squamous cell carcinoma were found （OR=5.77, 95%CI： 1.65-20.22）. Compared with the normal controls, the mRNA levels with Rsal polymorphism, Dral polymorphism, or any combined genotypes in cases showed no statistical difference.Conclusions This study suggests that carrying c2 allele and DD genotype conferreded an elevated risk for esophageal squamous cell carcinoma. There was no significant statistical relationship between the genotypes c1/c2, D/C, or the combined allele and mRNA expression.
