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Oxidative stress-mediated p53/p21WAF1/CIP1 pathway may be involved in microcystin-LR-induced cytotoxicity in HepG2 cells

Ma, Junguo, Li, Yuanyuan, Wu, Mengli, Li, Xiaoyu
Chemosphere 2018 v.194 pp. 773-783
apoptosis, catalase, cytotoxicity, dose response, glutathione, hepatotoxicity, human cell lines, malondialdehyde, microcystin-LR, oxidative stress, proto-oncogenes, superoxide dismutase
A previous study showed that microcystin-LR (MC-LR) exerted cytotoxicity and induced apoptosis in HepG2 cells. In the present study, we investigated whether oxidative stress-mediated p53/p21ᵂᴬF¹/Cᴵᴾ¹ is involved in this process to further elucidate the mechanism of cytotoxicity induced by MC-LR. Morphological evaluation showed that MC-LR induced time- and dose-dependent cytotoxicity in HepG2 cells. Biochemical assays revealed that MC-LR exposure altered the protein levels of HSP70 and HSP90, generally inhibited superoxide dismutase and catalase, reduced glutathione content, and increased the cellular malondialdehyde level of HepG2 cells, suggesting that MC-LR may induce biochemical disturbance and oxidative stress in HepG2 cells. The protein levels of p-p53 and p21 were markedly increased by MC-LR exposure in a concentration-dependent manner, suggesting that p53 and p21 may be involved in the process. Moreover, we also found that the proto-oncogene c-myc was significantly activated in HepG2 cells following MC-LR exposure, indicating that c-myc in HepG2 cells was potentially involved in response to MC-LR-induced apoptosis. These findings may contribute to further understanding the in vitro molecular mechanism of MC-LR hepatotoxicity.