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硫氧还蛋白和 HSP90 alpha 调节应激状态下褐点石斑鱼肝细胞中 ASK1-JNK1/2 信号通路。

Thioredoxin and HSP90 alpha modulate ASK1-JNK1/2 signaling in stressed hepatocytes of Mugil cephalus.

机构信息

Department of Biochemistry, Bharathi Women's College, Chennai-108, Tamilnadu, India.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2010 Mar;151(2):187-93. doi: 10.1016/j.cbpc.2009.10.004.

DOI:10.1016/j.cbpc.2009.10.004
PMID:19861173
Abstract

Induction of antioxidant proteins like thioredoxin (Trx) and heat shock protein 90 alpha (HSP90 alpha) is a crucial step in the cellular response to oxidative stress. Here, we report the impact of environmental stress on Trx and HSP90 alpha expressions in freshly isolated hepatocytes of Mugil cephalus living in either a contaminated (Test; Ennore) or uncontaminated (Control; Kovalam) estuary. Modulation in the activities of signal transduction molecules like apoptosis signal-regulating kinase 1 (ASK1) and c-Jun NH(2)-terminal kinase 1/2 (JNK1/2) were also investigated to understand their functional role under natural stressed condition. The expression pattern of the proteins was determined by immunoblotting and the relationship between the proteins was identified by regression analysis. Test fish hepatocytes demonstrated significant upregulation (P<0.05) in the levels of Trx and HSP90 alpha and insignificant inductions in the expression pattern of ASK1 and JNK1/2 than control fish hepatocytes. These findings provide direct evidence that Trx and HSP90 alpha induction in fish hepatocytes under stress may aid cell survival by negatively regulating ASK1 expression and thereby functionally antagonizing the apoptotic role of JNK1/2 in natural aquatic systems.

摘要

诱导抗氧化蛋白,如硫氧还蛋白(Trx)和热休克蛋白 90α(HSP90α),是细胞对氧化应激反应的关键步骤。在这里,我们报告了环境应激对生活在受污染(测试;恩诺尔)或未受污染(对照;科瓦兰)河口的 Mugil cephalus 新鲜分离肝细胞中 Trx 和 HSP90α表达的影响。还研究了信号转导分子如凋亡信号调节激酶 1(ASK1)和 c-Jun NH2-末端激酶 1/2(JNK1/2)的活性调节,以了解它们在自然应激条件下的功能作用。通过免疫印迹测定蛋白质的表达模式,并通过回归分析确定蛋白质之间的关系。与对照鱼肝细胞相比,测试鱼肝细胞中 Trx 和 HSP90α的水平显著上调(P<0.05),而 ASK1 和 JNK1/2 的表达模式则没有明显诱导。这些发现提供了直接证据,即在应激下鱼类肝细胞中 Trx 和 HSP90α的诱导可能通过负调节 ASK1 的表达来帮助细胞存活,从而在自然水生系统中发挥拮抗 JNK1/2 的凋亡作用。

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Heat-shock protein 90 alpha (HSP90α) modulates signaling pathways towards tolerance of oxidative stress and enhanced survival of hepatocytes of Mugil cephalus.
热休克蛋白 90 阿尔法(HSP90α)调节信号通路,使褐菖鲉的肝细胞耐受氧化应激并提高其存活率。
Cell Stress Chaperones. 2011 Jul;16(4):411-25. doi: 10.1007/s12192-011-0255-9. Epub 2011 Jan 28.