State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Toxicon. 2010 Dec;56(8):1334-41. doi: 10.1016/j.toxicon.2010.07.017. Epub 2010 Aug 3.
To investigate the effect of microcystin-LR (MC-LR) on apoptosis based on the endoplasmic reticulum stress (ERS) pathway in mouse liver and kidney, male ICR mice were intraperitoneally injected with 20 μg kg(-1) body weight MC-LR for 21 days, and mRNA and protein levels of ERS special molecules in liver and kidney were analyzed using quantitative real-time PCR and western blotting. MC-LR significantly improved mRNA and protein expression of C/EBP homologous protein (CHOP) and cleaved caspase-12 in liver, whereas it inhibited expression of CHOP and caspase-12 in kidney. MC-LR also induced significant down-regulation of B-cell lymphoma/leukemia-2 (Bcl-2) mRNA expression in liver and weak up-regulation in kidney. These results indicated the involvement of the ERS pathway in MC-LR-induced apoptosis of hepatic cells but not in renal cells of mice. The weight changes and histological damage of liver and kidney were in accordance with the appearance of ERS. Our results indicate that ERS plays an important role in hepatic cell apoptosis induced by MC-LR, and is considered as a new pathway of liver toxicity. Its relative special genes might be considered as potentially new biomarkers used for risk assessment of MC-LR in the environment.
为了研究微囊藻毒素-LR（MC-LR）通过内质网应激（ERS）通路对小鼠肝、肾细胞凋亡的影响，雄性 ICR 小鼠腹腔注射 20μg/kg 体重 MC-LR，连续 21 天，采用实时定量 PCR 和 Western blot 分析肝、肾组织中 ERS 特殊分子的 mRNA 和蛋白水平。MC-LR 显著上调了肝组织中 C/EBP 同源蛋白（CHOP）和裂解的胱天蛋白酶-12 的 mRNA 和蛋白表达，而对肾组织中 CHOP 和 caspase-12 的表达有抑制作用。MC-LR 还诱导了肝组织中 B 细胞淋巴瘤/白血病-2（Bcl-2）mRNA 表达的显著下调，而在肾组织中则表现为较弱的上调。这些结果表明 ERS 通路参与了 MC-LR 诱导的肝细胞核凋亡，但不参与肾细胞凋亡。肝、肾组织的体重变化和组织学损伤与 ERS 的出现相一致。我们的结果表明，ERS 在 MC-LR 诱导的肝细胞核凋亡中起重要作用，被认为是一种新的肝毒性途径。其相关的特殊基因可能被认为是环境中 MC-LR 风险评估的潜在新生物标志物。
