Psoralen induces hepatic toxicity through PERK and ATF6 related ER stress pathways in HepG2 cells

Toxicology Mechanisms and Methods
Yingli YuKun Zhou

Abstract

Psoralen has potential hepatotoxicity and has a certain promoting effect on the clinical liver injury of Psoralea corylifolia L (Fructus Psoraleae). This study investigated the underlying mechanisms of psoralen-induced hepatotoxicity in vitro. HepG2 cells were treated with psoralen for 6, 12, 24, or 48 h, and an endoplasmic reticulum (ER) stress-specific inhibitor, 4-PBA, was employed to investigate the mechanism of psoralen on ER stress and unfolded protein response (UPR). Cell viability was tested by MTT assay, ATP assay, and cell death by LDH. The apoptosis was reflected by the flow cytometry, caspase-8, and caspase-3 activates. The expression of ER stress-related markers was determined by RT-PCR and western blot. We found that psoralen significantly decreased cell viability, increased activities of caspase-8 and caspase-3, and upregulated expression of CHOP and BAX in a time- and dose-dependent manner. Moreover, psoralen significantly increased the expression and transcription levels of ER stress-related markers, including Grp78, PERK, eIF2α, ATF4, and ATF6, while IRE1α was not significantly affected. And 4-PBA could effectively inhibit psoralen-induced cell death and apoptosis along with the inhibition of ER stress respons...Continue Reading

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Citations

Oct 6, 2020·Frontiers in Pharmacology·Yali RenCheng Peng
Dec 16, 2020·Human & Experimental Toxicology·Juyang HuangKun Zhou
Dec 14, 2019·Chinese Journal of Natural Medicines·Qi-Hang ZhouGuang-Bo Ge
Mar 20, 2021·Journal of Molecular Neuroscience : MN·Liang HanYuxiu Shi

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