Lim I K, Park T J, Jee J W, Lee M S, Paik W K
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Korea.
J Cancer Res Clin Oncol. 1999 Aug-Sep;125(8-9):493-9. doi: 10.1007/s004320050307.
Differential expression of DNA-O6MeG: protein-L-cysteine S-methyltransferase (MGMT) activity and posttranslational modification of the protein during liver regeneration and carcinogenesis were compared in Sprague-Dawley male rats after partial hepatectomy and/or single i.p injection of diethylnitrosamine (DEN, 200 mg/kg). Regenerating hepatocytes after partial hepatectomy induced MGMT transiently within 3 days; however, the induction of MGMT was persistent for 2 weeks after DEN injection, and the combined treatment of DEN and partial hepatectomy maintained the elevated MGMT level for up to 4 weeks. The increased activity was transcriptionally regulated, when analyzed by Northern blot hybridization. The major active form of MGMT protein in the partially hepatectomized or DEN-treated rats was a 26-kDa or 24-kDa species respectively, which was confirmed by Western blot analysis and gel slice assay. The biological significance of the differential induction of MGMT during partial hepatectomy or DEN-induced carcinogenesis is not obvious; however, further studies on possible posttranslational modifications of MGMT protein might shed some light on the functional aspect of MGMT induction.
在部分肝切除和/或单次腹腔注射二乙基亚硝胺（DEN，200 mg/kg）后的Sprague-Dawley雄性大鼠中，比较了DNA-O6甲基鸟嘌呤：蛋白质-L-半胱氨酸S-甲基转移酶（MGMT）活性的差异表达以及肝脏再生和致癌过程中该蛋白质的翻译后修饰。部分肝切除后的再生肝细胞在3天内短暂诱导MGMT；然而，DEN注射后MGMT的诱导持续2周，DEN与部分肝切除的联合治疗使MGMT水平升高维持长达4周。通过Northern印迹杂交分析，活性增加是由转录调控的。部分肝切除或DEN处理的大鼠中MGMT蛋白的主要活性形式分别为26 kDa或24 kDa，这通过Western印迹分析和凝胶切片测定得到证实。在部分肝切除或DEN诱导的致癌过程中MGMT差异诱导的生物学意义尚不明显；然而，对MGMT蛋白可能的翻译后修饰的进一步研究可能会揭示MGMT诱导的功能方面。
