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应激鱼类肝细胞中ERK上调过程中HO-1和CYP1A2的差异表达。

Differential expression of HO-1 and CYP1A2 during up-regulation of ERK in stressed fish hepatocytes.

作者信息

Padmini Ekambaram, Tharani Jayachandran

机构信息

P.G. Department of Biochemistry, Bharathi Women's College, Affiliated to University of Madras, Chennai, 600108, Tamil Nadu, India,

出版信息

Environ Monit Assess. 2015 Jan;187(1):4147. doi: 10.1007/s10661-014-4147-1. Epub 2014 Dec 4.

DOI:10.1007/s10661-014-4147-1
PMID:25471622
Abstract

Induction of heme oxygenase-1 (HO-1) and extracellular signal-regulated kinase (ERK) is a crucial step in the cellular response to oxidative stress. Altered expression of such proteins in response to stress conditions is a key factor for the maintenance of cellular integrity and survival. Hypoxia-inducible factor-1 (HIF-1) and cytochrome P450 1A (CYP1A) are critical indicators of environmental exposure to hypoxia. The current study was aimed to analyse the expression pattern of HO-1, p-ERK, HIF-1α and CYP1A2 in hepatocytes of Mugil cephalus inhabiting Kovalam (unpolluted site) and Ennore (polluted site) estuaries. The impact of stress on hepatocytes was assessed by measuring the level of lipid hydroperoxides (LHP) and reduced glutathione (GSH) in hepatocytes of M. cephalus inhabiting these estuaries. The expression of HO-1, p-ERK, HIF-1α and CYP1A2 was analysed by ELISA and immunoblot analysis, respectively. There was significant decrease of GSH (19%) and CYP1A2 (34%) along with significant increase of LHP (31%), HO-1 (96%), p-ERK (p < 0.01) and HIF-1α (41%) in hepatocytes of M. cephalus inhabiting Ennore estuary than Kovalam estuary. The present study shows that increased synthesis of HO-1 mainly regulated by p-ERK and HIF-1α may significantly contribute to the environmental adaptation processes of grey mullet, by protecting the cells from oxidative stress and stress-induced degenerative changes.

摘要

血红素加氧酶-1(HO-1)和细胞外信号调节激酶(ERK)的诱导是细胞对氧化应激反应的关键步骤。这些蛋白质在应激条件下表达的改变是维持细胞完整性和存活的关键因素。缺氧诱导因子-1(HIF-1)和细胞色素P450 1A(CYP1A)是环境暴露于缺氧的关键指标。本研究旨在分析居住在科瓦拉姆(未受污染地点)和埃努雷(污染地点)河口的鲻鱼肝细胞中HO-1、p-ERK、HIF-1α和CYP1A2的表达模式。通过测量居住在这些河口的鲻鱼肝细胞中脂质氢过氧化物(LHP)和还原型谷胱甘肽(GSH)的水平来评估应激对肝细胞的影响。分别通过ELISA和免疫印迹分析来分析HO-1、p-ERK、HIF-1α和CYP1A2的表达。与居住在科瓦拉姆河口的鲻鱼相比,居住在埃努雷河口的鲻鱼肝细胞中GSH(19%)和CYP1A2(34%)显著降低,同时LHP(31%)、HO-1(96%)、p-ERK(p < 0.01)和HIF-1α(41%)显著增加。本研究表明,主要由p-ERK和HIF-1α调节的HO-1合成增加可能通过保护细胞免受氧化应激和应激诱导的退行性变化,对鲻鱼的环境适应过程做出显著贡献。

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