Differential regulation of antioxidant enzymes in response to oxidants.
Differential regulation of antioxidant enzymes in response to oxidants.
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DOI：
10.1016/s0021-9258(18)54242-3
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发表时间：
1991-12
期刊：
影响因子：
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通讯作者：
S. Shull;Nicholas H. Heintz;Muthu Periasamy;M. Manohar;Yvonne W. M. Janssen;J. Marsh;Brooke T. Mossman-Brooke-T
中科院分区：
文献类型：
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作者：
S. Shull;Nicholas H. Heintz;Muthu Periasamy;M. Manohar;Yvonne W. M. Janssen;J. Marsh;Brooke T. Mossman-Brooke-T
我们已经证明了锰超氧化物歧化酶（MnSOD）或过氧化氢酶mRNA的选择性诱导暴露后的气管支气管上皮细胞在体外不同的氧化应激。此外，H2 O2引起的剂量依赖性增加过氧化氢酶mRNA在指数增长和汇合的细胞。在250 μ M H2 O2的无毒剂量下观察到过氧化氢酶mRNA的3倍诱导。谷胱甘肽过氧化物酶（GPX）和MnSOD的稳态mRNA水平的增加不太引人注目。过氧化氢酶，锰超氧化物歧化酶，和GPX mRNA的表达最高的融合细胞。与此相反，铜和锌SOD（CuZnSOD）的mRNA的组成型表达是最大的分裂细胞和H2 O2在指数增长和汇合的细胞不受影响。MnSOD mRNA选择性诱导融合上皮细胞暴露于活性氧生成系统，黄嘌呤/黄嘌呤氧化酶，而稳态水平的GPX，过氧化氢酶，CuZnSOD mRNA保持不变。MnSOD mRNA的3倍诱导呈剂量依赖性，在0.2单位/ml黄嘌呤氧化酶时达到峰值。MnSOD mRNA的表达早在2 h就开始增加，24 h达到最大诱导。免疫反应性MnSOD蛋白产生相应的剂量和时间依赖性的方式。MnSOD基因表达的诱导被放线菌素D和放线菌酮阻止。这些数据表明，呼吸道上皮细胞通过选择性诱导某些抗氧化酶来响应不同的氧化剂损伤。因此，抗氧化酶的基因表达在这些细胞类型中似乎不受协调调节。
We have demonstrated the selective induction of manganese superoxide dismutase (MnSOD) or catalase mRNA after exposure of tracheobronchial epithelial cells in vitro to different oxidant stresses. Addition of H2O2 caused a dose-dependent increase in catalase mRNA in both exponentially growing and confluent cells. A 3-fold induction of catalase mRNA was seen at a nontoxic dose of 250 microM H2O2. Increase in the steady-state mRNA levels of glutathione peroxidase (GPX) and MnSOD were less striking. Expression of catalase, MnSOD, and GPX mRNA was highest in confluent cells. In contrast, constitutive expression of copper and zinc SOD (CuZnSOD) mRNA was greatest in dividing cells and was unaffected by H2O2 in both exponentially growing and confluent cells. MnSOD mRNA was selectively induced in confluent epithelial cells exposed to the reactive oxygen species-generating system, xanthine/xanthine oxidase, while steady-state levels of GPX, catalase, and CuZnSOD mRNA remained unchanged. The 3-fold induction of MnSOD mRNA was dose-dependent, reaching a peak at 0.2 unit/ml xanthine oxidase. MnSOD mRNA increases were seen as early as 2 h and reached maximal induction at 24 h. Immunoreactive MnSOD protein was produced in a corresponding dose- and time-dependent manner. Induction of MnSOD gene expression was prevented by addition of actinomycin D and cycloheximide. These data indicate that epithelial cells of the respiratory tract respond to different oxidant insults by selective induction of certain antioxidant enzymes. Hence, gene expression of antioxidant enzymes does not appear to be coordinately regulated in these cell types.