Wong G H, Goeddel D V
Department of Molecular Biology, Genentech, San Francisco, CA 94080.
Science. 1988 Nov 11;242(4880):941-4. doi: 10.1126/science.3263703.
Manganous superoxide dismutase (MnSOD) scavenges potentially toxic superoxide radicals produced in the mitochondria. Tumor necrosis factor-alpha (TNF-alpha) was found to induce the messenger RNA for MnSOD, but not the mRNAs for other antioxidant or mitochondrial enzymes tested. The increase in MnSOD mRNA occurred rapidly and was blocked by actinomycin D, but not by cycloheximide. Induction of MnSOD mRNA was also observed with TNF-beta, interleukin-1 alpha (IL-1 alpha), and IL-1 beta but not with other cytokines or agents tested. TNF-alpha induced MnSOD mRNA in all cell lines and normal cells examined in vitro and in various organs of mice in vivo. These effects of TNF-alpha and IL-1 on target cells may contribute to their reported protective activity against radiation as well as their ability to induce resistance to cell killing induced by the combination of TNF-alpha and cycloheximide.
锰超氧化物歧化酶（MnSOD）可清除线粒体中产生的具有潜在毒性的超氧自由基。研究发现，肿瘤坏死因子-α（TNF-α）可诱导MnSOD的信使核糖核酸（mRNA）生成，但对其他所检测的抗氧化剂或线粒体酶的mRNA无此作用。MnSOD mRNA的增加迅速，且被放线菌素D阻断，但不被放线菌酮阻断。用TNF-β、白细胞介素-1α（IL-1α）和IL-1β也观察到了MnSOD mRNA的诱导，但其他所检测的细胞因子或试剂则无此作用。TNF-α在体外检测的所有细胞系和正常细胞以及体内小鼠的各种器官中均诱导MnSOD mRNA生成。TNF-α和IL-1对靶细胞的这些作用可能有助于它们所报道的抗辐射保护活性以及诱导对TNF-α和放线菌酮联合诱导的细胞杀伤产生抗性的能力。
