MANGANESE SUPEROXIDE-DISMUTASE - A HEPATIC ACUTE PHASE PROTEIN REGULATED BY INTERLEUKIN-6 AND GLUCOCORTICOIDS
MANGANESE SUPEROXIDE-DISMUTASE - A HEPATIC ACUTE PHASE PROTEIN REGULATED BY INTERLEUKIN-6 AND GLUCOCORTICOIDS
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DOI：
10.1210/endo-129-5-2376
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发表时间：
1991-11-01
期刊：
影响因子：
4.8
通讯作者：
NICK, HS
中科院分区：
文献类型：
--
作者：
DOUGALL, WC;NICK, HS
超氧化物歧化酶（SOD）是一类重要的金属酶，它对超氧化物自由基进行还原和歧化。它们被认为是抗氧化防御系统中的主要酶。识别控制SOD基因转录的刺激物对于理解SOD基因调控是必不可少的。在这项研究中，我们表明，锰超氧化物歧化酶（MnSOD）的mRNA水平升高的脂多糖，细菌内毒素，在大鼠肝脏。然而，无论是脂多糖，也没有肿瘤坏死因子-α在培养的原代肝细胞MnSOD mRNA表达的影响。另一方面，炎症细胞因子，白细胞介素-1（IL-1）和IL-6确实增加MnSOD的mRNA水平，无论是2或15倍，分别在20小时内，在肝细胞。IL-6诱导的MnSOD mRNA水平的增加被地塞米松（一种糖皮质激素）减弱，在肝细胞培养少于16 h。相比之下，在最初培养超过16小时的肝细胞中，IL-6和地塞米松协同增加MnSOD mRNA水平。MnSOD表达的IL-6，这是一种已知的炎症细胞因子的诱导，表明MnSOD可能在炎症过程中发挥作用。由于已知炎症会导致细胞的氧化损伤，MnSOD的作用可能是保护细胞免受炎症介导的氧化损伤。
The superoxide dismutases (SODs) are important metallo-enzymes which scavenge and dismutate the superoxide free radical. They are thought to be the main enzymes in the antioxidant defense system. Identification of stimuli that control transcription of the SOD genes is essential for understanding SOD gene regulation. In this study we show that manganese SOD (MnSOD) mRNA levels are elevated by lipopolysaccharide, a bacterial endotoxin, in rat liver. However, neither lipopolysaccharide nor tumor necrosis factor-alpha had an effect on MnSOD mRNA expression in cultured primary hepatocytes. On the other hand, the inflammatory cytokines, interleukin-1 (IL-1) and IL-6 did increase MnSOD mRNA levels, either 2- or 15-fold, respectively, over a 20-h period in hepatocytes. The IL-6-induced increase in MnSOD mRNA levels was attenuated by dexamethasone, a glucocorticoid, in hepatocytes cultured for less than 16 h. In contrast, in hepatocytes originally cultured for more than 16 h, IL-6 and dexamethasone produced a synergistic increase in MnSOD mRNA levels. The induction of MnSOD expression by IL-6, which is a known inflammatory cytokine, suggests that MnSOD may play a role in the inflammation process. Since inflammation is known to result in oxidative damage to cells, the role of MnSOD may be to protect cells from inflammation-mediated oxidative damage.