Induction of mnsod gene by arachidonic acid is mediated by reactive oxygen species and p38 MAPK signaling pathway in human HepG2 hepatoma cells
Induction of mnsod gene by arachidonic acid is mediated by reactive oxygen species and p38 MAPK signaling pathway in human HepG2 hepatoma cells
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DOI：
10.1016/s0891-5849(02)00834-1
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发表时间：
2002-06-01
影响因子：
7.4
通讯作者：
Dauça, M
中科院分区：
文献类型：
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作者：
Bianchi, A;Bécuwe, P;Dauça, M
花生四烯酸(AA)的代谢通过产生活性氧在不同类型的细胞中诱导氧化应激。由于后者可能被抗氧化酶如锰和铜/锌依赖的超氧化物歧化酶(分别为MnSOD和铜/锌超氧化物歧化酶)清除，我们研究了AA对其在人肝癌细胞中表达的影响。RT-PCR法和Western印迹法检测结果表明，AA诱导了MnSOD在mRNA和蛋白水平的表达增加，但对铜/锌超氧化物歧化酶的表达无明显影响。这种诱导也表现为MnSOD活性的增加。AA和放线菌素D共同作用于HepG2细胞，证明AA诱导的MnSOD表达需要从头转录。5，8，11，14-二十碳四烯酸(AA的非代谢类似物)或AA代谢途径的不同抑制剂培养的HepG2细胞不能诱导MnSOD的表达，这表明AA的代谢是必需的。对AA诱导MnSOD表达机制的进一步研究表明，AA代谢释放的超氧阴离子通过涉及蛋白激酶C和p38丝裂原活化蛋白激酶(MAPK)的信号控制途径发挥第二信使的作用。这些结果确定了P39 MAPK依赖通路在MnSOD基因调控中的新作用。(C)2002年爱思唯尔科学公司。
Metabolism of arachidonic acid (AA) is known to induce in different cell types an oxidative stress via the production of reactive oxygen species. As these latter may be scavenged by antioxidant enzymes as manganese and copper/zine-dependent superoxide dismutase (MnSOD and Cu/ZnSOD, respectively), we investigated the effects of AA on their expression in human HepG2 hepatoma cells. RT-PCR and Western blot data revealed that AA induced an increase in the MnSOD, but not Cu/ZnSOD, expression at the mRNA and protein levels, respectively. This induction was also marked by an increase in MnSOD activity. The AA-induced MnSOD expression required de novo transcription as demonstrated by cotreatment of HepG2 cells with AA and actinomycin D. The fact that MnSOD expression was not induced when HepG2 cells were cultured with 5,8,11,14-eicosatetraynoic acid (ETYA), a nonmetabolizable analog of AA, or with different inhibitors of the AA metabolism pathways suggested that the metabolism of AA was required. Further investigations into the mechanisms by which AA induced MnSOD expression showed that superoxide anions released from AA metabolism act as second messengers via a signal-controlling pathway involving protein kinase C and p38 mitogen activated protein kinase (MAPK). These results define a novel role of p39 MAPK dependent-pathway in the regulation of MnSOD gene. (C) 2002 Elsevier Science Inc.