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Crosstalk between heat shock proteins, NRF2, NF-κB and different endogenous antioxidants during lead-induced hepatotoxicity in Puntius ticto
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2021-02-04 , DOI: 10.1016/j.aquatox.2021.105771
Saheli Kumar , Mahammed Moniruzzaman , Anindita Chakraborty , Adity Sarbajna , Suman Bhusan Chakraborty

Present study aims to investigate interaction of molecular chaperons (heat shock protein 70, heat shock protein 90) with transcriptional factors (nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) to evaluate their role during metal induced stress in fish hepatocytes. Adult Puntius ticto were exposed to lead nitrate at 0 mg/l (control), 1/50th (0.04 mg/l) and 1/20th (0.12 mg/l) of LC50 for 30 days and sacrificed to collect liver tissues. Activity of selected liver enzymes, antioxidants and metallothionein were analyzed. Levels of heat shock protein 70, heat shock protein 90, nuclear factor kappa B, nuclear factor E2-related factor 2 and Kelch-like ECH-associated protein 1 were also measured. Liver enzymes showed a significant increase (p < 0.05) in both Pb exposed groups indicating that the liver might be at risk of damage. Increased level of lipid peroxidation due to metal stress was marked by significant increase (p < 0.05) in malondialdehyde level in fish exposed to the higher Pb concentration compared to control (+ 13.7 %). Significant increase (p < 0.05) in gluthathione reductase (+ 35 %, + 39.2 %), glutathione s-transferase (+ 22.4 %, + 50.4 %) activities and decrease in reduced glutathione level (− 6.75 %, − 12.25 %) in fish exposed to both lower and higher Pb concentration compared to control also indicated metal induced oxidative damage in fish liver. Super oxide dismutase and catalase activities increased significantly (p < 0.05) during exposure to lower Pb concentration, while decreased significantly (p < 0.05) during exposure to higher Pb concentration compared to those in control. Significant (P < 0.05) increase (+ 52.63 %, + 89.47 %) in metallothionein in Pb exposed groups confirmed its role in detoxification process of the metal. Heat shock protein 70 and heat shock protein 90 expression levels increased significantly (p < 0.05) during metal exposure indicating their role as modulator of stress-induced antioxidant protein remodelling. A positive correlation between nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1 with gluthathione regulatory enzymes (gluthathione reductase and glutathione s-transferase) was noted. Current study effectively illuminates the critical role of different factors (heat shock proteins/nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) to influence the expression and synthesis of antioxidants and other functional enzymes in lead-exposed fish liver.



中文翻译:

在铅-诱导的肝毒性期间的热休克蛋白,NRF2,NF-κB和不同的内源性抗氧化剂之间的串扰Puntius ticto

本研究旨在研究分子伴侣(热激蛋白70,热激蛋白90)与转录因子(核因子κB/核因子E2相关因子2 / Kelch样ECH相关蛋白1)的相互作用,以评估其作用。在金属诱导的鱼肝细胞应激过程中。成年的Puntius ticto暴露于LC 50浓度为0 mg / l(对照),1/50(0.04 mg / l)和1/20(0.12 mg / l)的硝酸铅中30天并处死以收集肝组织。分析了选定的肝酶,抗氧化剂和金属硫蛋白的活性。还测量了热休克蛋白70,热休克蛋白90,核因子κB,核因子E2相关因子2和Kelch样ECH相关蛋白1的水平。在两个暴露于铅的人群中,肝酶均显着增加(p <0.05),表明肝脏可能有受损的风险。与对照相比,暴露于较高Pb浓度的鱼中丙二醛含量显着增加(p <0.05),这是由于金属胁迫引起的脂质过氧化水平增加的标志。谷胱甘肽还原酶(+ 35%,+ 39.2%),谷胱甘肽s-转移酶(+ 22.4%,+ 50.4%)活性显着增加(p <0.05)和降低的谷胱甘肽水平降低(− 6.75%,− 12。与对照相比,暴露于较低和较高Pb浓度的鱼中有25%的鱼也表明金属诱导了鱼肝中的氧化损伤。与对照相比,暴露于较低Pb浓度时,超氧化物歧化酶和过氧化氢酶活性显着增加(p <0.05),而暴露于较高Pb浓度时,超氧化物歧化酶和过氧化氢酶活性显着降低(p <0.05)。铅暴露组的金属硫蛋白显着增加(P <0.05)(+ 52.63%,+ 89.47%),证实了其在金属解毒过程中的作用。在金属暴露期间,热休克蛋白70和热休克蛋白90的表达水平显着增加(p <0.05),表明它们作为应激诱导的抗氧化蛋白重塑的调节剂。注意到核因子κB/核因子E2相关因子2 / Kelch样ECH相关蛋白1与谷胱甘肽调节酶(谷胱甘肽还原酶和谷胱甘肽S-转移酶)呈正相关。当前的研究有效地阐明了不同因素(热休克蛋白/核因子κB/核因子E2相关因子2 / Kelch样ECH相关蛋白1)在抗氧化剂和其他功能性酶的表达和合成中的关键作用。铅暴露的鱼肝。

更新日期:2021-02-09
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