Manganese superoxide dismutase is induced by endoplasmic reticulum stress through IRE1-mediated nuclear factor (NF)-κB and AP-1 activation
Manganese superoxide dismutase is induced by endoplasmic reticulum stress through IRE1-mediated nuclear factor (NF)-κB and AP-1 activation
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DOI：
10.1248/bpb.27.1202
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发表时间：
2004-08-01
影响因子：
2
通讯作者：
Nomura, Y
中科院分区：
文献类型：
--
作者：
Kaneko, M;Takahashi, T;Nomura, Y
锰超氧化物歧化酶（MnSOD）是一种清除超氧自由基的抗氧化酶，位于线粒体基质中。MnSOD是通过核因子（NF）-kappaB和AP-1激活由各种刺激诱导的。我们研究了锰超氧化物歧化酶在HeLa细胞中的表达，暴露于各种干扰内质网（ER）功能的药物。所有的代理引起的MnSOD的mRNA和蛋白水平的增加。尽管内质网应激相关转录因子ATF 6、IRE 1和XBP 1通常上调内质网应激反应基因，但这两种分子的过表达均不影响MnSOD的mRNA和蛋白水平。此外，我们发现ER应激试剂诱导NF-κ B和AP-1活化，而这两种活化被显性阴性IRE 1突变体抑制。我们最终证明，ER应激诱导的MnSOD表达减少IRE 1突变体。这些结果表明，MnSOD的表达是由ER应激通过IR-E1介导的NF-κ B和AP-1激活来控制的。
Manganese superoxide dismutase (MnSOD) is an antioxidative enzyme that scavenges superoxide radicals and is localized in the mitochondrial matrix. MnSOD is induced by a variety of stimuli through nuclear factor (NF)-kappaB and AP-1 activation. We investigated the expression of MnSOD in HeLa cells exposed to various agents interfering with endoplasmic reticulum (ER) functions. All agents caused an increase in the mRNA and protein levels of MnSOD. Although ER stress-responsive genes often are up-regulated by ATF6, IRE1 and XBP1, which are ER stress-related transcription factors/transducers, the overexpression of neither molecule affected the levels of MnSOD mRNA and protein. Furthermore, we showed that ER stress reagents induced NF-kappaB and AP-1 activation that were inhibited by a dominant-negative IRE1 mutant. We finally demonstrated that ER stress-induced MnSOD expression was reduced by the IRE1 mutant. These results suggest that the MnSOD expression is controlled by ER stress through IR-E1-mediated NF-kappaB and AP-1 activation.