Sato M, Sasaki M, Hojo H
Department of Biomolecular Sciences, Fukushima Medical College, Japan.
Arch Biochem Biophys. 1995 Feb 1;316(2):738-44. doi: 10.1006/abbi.1995.1098.
Antioxidative roles of metallothionein (MT) and manganese superoxide dismutase (Mn-SOD) induced by tumor necrosis factor (TNF) and interleukin 6 (IL-6) have been studied. Since pretreatment of rat with dexamethasone, an inhibitor of cytokine production, prevented MT synthesis induced by paraquat which is a typical superoxide generator, MT synthesis by oxidative stress may be, at least partly, mediated through cytokines. Pretreatment of rat with TNF or IL-6 prevented liver damage and lipid peroxidation caused by carbon tetrachloride. Administration of TNF increased activity of mitochondrial Mn-SOD and concentrations of cytoplasmic MT, but not activities of glutathione peroxidases and Cu,Zn-SOD in the liver. The increment of the Mn-SOD activity and MT was due to the de novo protein synthesis, because gene expression of mRNAs of Mn-SOD and MT in the liver was also induced by TNF and IL-6. These data strongly suggest that MT and Mn-SOD in the liver cooperatively play antioxidative roles. Pretreatment with TNF, however, did not affect the increased levels of plasma fibrinogen and liver MT induced by the following paraquat treatment, although it did prevent lipid peroxidation in the liver. The data suggest that MT is not directly induced by oxygen free radicals. Cytokines may be released by paraquat in tissues other than the liver and induce hepatic synthesis of acute phase proteins including fibrinogen, MT, and Mn-SOD. MT and Mn-SOD induced by cytokines in the liver exert an antioxidative role during acute phase response, therefore preventing tissues from injury by oxidative stress.
肿瘤坏死因子（TNF）和白细胞介素6（IL-6）诱导的金属硫蛋白（MT）和锰超氧化物歧化酶（Mn-SOD）的抗氧化作用已得到研究。由于用细胞因子产生抑制剂地塞米松预处理大鼠可阻止百草枯（一种典型的超氧化物产生剂）诱导的MT合成，因此氧化应激诱导的MT合成可能至少部分是通过细胞因子介导的。用TNF或IL-6预处理大鼠可预防四氯化碳引起的肝损伤和脂质过氧化。给予TNF可增加肝脏线粒体Mn-SOD的活性和细胞质MT的浓度，但不增加肝脏中谷胱甘肽过氧化物酶和铜锌超氧化物歧化酶的活性。Mn-SOD活性和MT的增加是由于从头合成蛋白质，因为TNF和IL-6也可诱导肝脏中Mn-SOD和MT的mRNA基因表达。这些数据有力地表明肝脏中的MT和Mn-SOD协同发挥抗氧化作用。然而，尽管TNF预处理可预防肝脏中的脂质过氧化，但它并不影响随后百草枯处理诱导的血浆纤维蛋白原和肝脏MT水平的升高。数据表明MT不是由氧自由基直接诱导的。细胞因子可能由肝脏以外的组织中的百草枯释放，并诱导包括纤维蛋白原、MT和Mn-SOD在内的急性期蛋白的肝脏合成。细胞因子在肝脏中诱导的MT和Mn-SOD在急性期反应中发挥抗氧化作用，从而防止组织受到氧化应激的损伤。
