Endoplasmic reticulum stress in murine liver and kidney exposed to microcystin-LR.
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.
Qin
Wendi
W
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Xu
Lizhi
L
Zhang
Xuxiang
X
Wang
Yaping
Y
Meng
Xiaoyang
X
Miao
Aijun
A
Yang
Liuyan
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000648:ultrastructure; D000091342:Endoplasmic Reticulum Chaperone BiP; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008387:Marine Toxins; D051379:Mice; D008813:Mice, Inbred ICR; D052998:Microcystins / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism
C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D008387:Marine Toxins; D052998:Microcystins; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D053454:Caspase 12; C057862:cyanoginosin LR