Hif1α Mediated Ho-1 Expression in Fish Adipocytes: Role of Hypoxia In Ennore Estuary

P. Ekambaram, P. Parasuraman
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引用次数: 1

Abstract

Heme oxygenase-1 (HO-1), an inducible stress protein; is involved in the regulation of adipogenesis, cellular bioenergetics and cytoprotective mechanism against hypoxia induced oxidative stress. Polluted aquatic environment leads to large oxygen fluctuations which may cause alteration in fish adaptation mechanism by HIF1α regulation. Environmental pollutants have a high tendency to accumulate, persist and bio-concentrate in adipocytes due to its lipophilic nature which ultimately causes adipocytes hypoxia that in turn affects metabolic energy balance. CYP1A2 and HO-1 are the chief detoxifying and cytoprotective enzymes involved in the oxidative metabolism of a wide variety of pollutants and its mediated cytotoxic products. The key role of hypoxia and its mediated signaling protein changes in fish adipocytes due to low dissolved oxygen in Ennore estuary was demonstrated in our previous work. Therefore, we analyzed the effect of pollutants induced hypoxia by assessing CD, HNE, TAC, G3PDH, ATP, HIF1α, HO-1 and CYP1A2 in fish adipocytes of control/unpolluted site and test/polluted site. Increase in CD, HNE, HIF1α, HO-1 along with a decrease in TAC, G3PDH, ATP and CYP1A2 observed in test adipocytes. From the results achieved, it shows that induction of HO-1 by HIF1α is crucial in maintaining the cell integrity to secure adipocytes and its maturation in the fish collected from the hypoxic environment. This study also highlights the role of HIF1α and HO-1 in regulating the expression of CYP1A2 during pollutants induced hypoxic condition.
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hf1α介导的Ho-1在鱼类脂肪细胞中的表达:缺氧在enore河口的作用
血红素加氧酶-1 (HO-1),诱导应激蛋白;参与脂肪形成的调控、细胞生物能量学和抗缺氧诱导氧化应激的细胞保护机制。受污染的水生环境会导致大范围的氧波动,从而可能导致鱼类通过HIF1α调控的适应机制发生改变。环境污染物由于其亲脂性,极易在脂肪细胞内积累、滞留和生物浓缩,最终导致脂肪细胞缺氧,进而影响代谢能量平衡。CYP1A2和HO-1是主要的解毒和细胞保护酶,参与多种污染物及其介导的细胞毒性产物的氧化代谢。我们在之前的工作中已经证明了低溶解氧在enore河口鱼类脂肪细胞中缺氧及其介导的信号蛋白变化的关键作用。因此,我们通过检测对照/未污染区和试验/污染区鱼类脂肪细胞的CD、HNE、TAC、G3PDH、ATP、HIF1α、HO-1和CYP1A2,分析污染物对缺氧的影响。实验脂肪细胞中CD、HNE、HIF1α、HO-1升高,TAC、G3PDH、ATP、CYP1A2降低。从所取得的结果来看,它表明HIF1α诱导HO-1对于维持细胞完整性以确保脂肪细胞及其在缺氧环境中成熟至关重要。本研究还强调了HIF1α和HO-1在污染物诱导的缺氧条件下调节CYP1A2表达的作用。
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