Jang Byeong-Churl, Paik Ji-Hye, Kim Sang-Pyo, Shin Dong-Hoon, Song Dae-Kyu, Park Jong-Gu, Suh Min-Ho, Park Jong-Wook, Suh Seong-Il
Chronic Disease Research Center and Institute for Medical Science, Keimyung University School of Medicine, #194 DongSan-Dong, Jung-Gu, Daegu 700-712, South Korea.
Cell Signal. 2005 May;17(5):625-33. doi: 10.1016/j.cellsig.2004.10.001.
Catalase induces COX-2 or iNOS expression in some type of cells, but the mechanism remains unclear. Here we investigated the effect of catalase on COX-2 and iNOS expression in BV2 microglia and the inductive mechanism associated. Exposure of catalase to BV2 microglia induced expression of COX-2 and iNOS that was related with transcriptional up-regulation. Importantly, catalase-induced COX-2 and iNOS expression needed activations of NF-kappaB, PI3K/AKT, and JNKs, which were important for the transcriptional up-regulation of COX-2 and iNOS. Notably, rapamycin inhibition of p70S6K led to down-regulation of COX-2 and iNOS protein expression, but not steady-state mRNA expression and transcription, induced by catalase, suggesting that p70S6K is involved in increased COX-2 and iNOS mRNA translation by catalase. Interestingly, there was PI3K-dependent activation of AKT, p70S6K, JNKs, and NF-kappaB in response to catalase. These data collectively suggest catalase-induced COX-2 and iNOS expression in BV2 microglia is, in part at least, mediated through activation of multiple signaling proteins.
过氧化氢酶可诱导某些类型细胞中COX - 2或iNOS的表达,但其机制尚不清楚。在此,我们研究了过氧化氢酶对BV2小胶质细胞中COX - 2和iNOS表达的影响及其相关诱导机制。将过氧化氢酶作用于BV2小胶质细胞可诱导COX - 2和iNOS的表达,这与转录上调有关。重要的是,过氧化氢酶诱导的COX - 2和iNOS表达需要NF - κB、PI3K/AKT和JNKs的激活,这些对于COX - 2和iNOS的转录上调很重要。值得注意的是,雷帕霉素对p70S6K的抑制导致过氧化氢酶诱导的COX - 2和iNOS蛋白表达下调,但不影响其稳态mRNA表达和转录,这表明p70S6K参与了过氧化氢酶增加COX - 2和iNOS mRNA的翻译过程。有趣的是,对过氧化氢酶的反应存在PI3K依赖性的AKT、p70S6K、JNKs和NF - κB的激活。这些数据共同表明,过氧化氢酶诱导BV2小胶质细胞中COX - 2和iNOS的表达至少部分是通过多种信号蛋白的激活介导的。