title: Endoplasmic reticulum stress is involved in 2,4-dichlorophenol-induced hepatotoxicity.
abstract: 2,4-Dichlorophenol (2,4-DCP) is an environmental pollutant exhibiting a wide spectrum of toxic effects. We investigated the toxic effects and potential mechanisms underlying 2,4-DCP-induced hepatotoxicity. In vitro, 2,4-DCP caused hepatotoxicity manifested by a decrease in cell viability and inhibition of colony formation. Bip and CHOP expression was up-regulated at the mRNA and protein levels. Moreover, 2,4-DCP induced eIF2α phosphorylation and Xbp1 mRNA splicing, indicating that endoplasmic reticulum (ER) stress was activated after exposure of HL7702 cells to 2,4-DCP for 12 hr. Furthermore, the mitochondrial membrane potential collapsed and apoptosis was triggered after exposure to 2,4-DCP for 24 hr. In vivo, 2,4-DCP caused histological changes in the liver, and dramatically elevated the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels of mice. ER stress was also triggered in the liver of mice on days 1 and 3. The ER stress inhibitor TUDCA could partly relieve the liver damage, as indicated by the restoration of serum ALT and AST levels. Taken together, our results demonstrated that ER stress may serve as an early warning mechanism against 2,4-DCP-induced hepatotoxicity, and severe ER stress may lead to apoptosis.
authors.affiliation: Institute of Life Science, Nanchang University, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Fu
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002733:Chlorophenols / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000071717:X-Box Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D002733:Chlorophenols; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D004785:Environmental Pollutants; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051742:Transcription Factor CHOP; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C004762:2,4-dichlorophenol