title: Sodium tauroursodeoxycholate prevents paraquat-induced cell death by suppressing endoplasmic reticulum stress responses in human lung epithelial A549 cells.
abstract: Paraquat is a commonly used herbicide; however, it is highly toxic to humans and animals. Exposure to paraquat causes severe lung damage, leading to pulmonary fibrosis. However, it has not been well clarified as how paraquat causes cellular damage, and there is no established standard therapy for paraquat poisoning. Meanwhile, endoplasmic reticulum stress (ERS) is reported to be one of the causative factors in many diseases, although mammalian cells have a defense mechanism against ERS-induced apoptosis (unfolded protein response). Here, we demonstrated that paraquat changed the expression levels of unfolded protein response-related molecules, resulting in ERS-related cell death in human lung epithelial A549 cells. Moreover, treatment with sodium tauroursodeoxycholate (TUDCA), a chemical chaperone, crucially rescued cells from death caused by exposure to paraquat. These results indicate that paraquat toxicity may be associated with ERS-related molecules/events. Through chemical chaperone activity, treatment with TUDCA reduced paraquat-induced ERS and mildly suppressed cell death. Our findings also suggest that TUDCA treatment represses the onset of pulmonary fibrosis caused by paraquat, and therefore chemical chaperones may have novel therapeutic potential for the treatment of paraquat poisoning.
authors: Department of Pharmacy, Kyoto University Hospital, Kyoto 606-8507, Japan.
authors: Tomohiro
authors: T
authors: Omura
authors: Masaru
authors: M
authors: Asari
authors: Joe
authors: J
authors: Yamamoto
authors: Kumiko
authors: K
authors: Oka
authors: Chisato
authors: C
authors: Hoshina
authors: Chikatoshi
authors: C
authors: Maseda
authors: Toshio
authors: T
authors: Awaya
authors: Yoshikazu
authors: Y
authors: Tasaki
authors: Hiroshi
authors: H
authors: Shiono
authors: Atsushi
authors: A
authors: Yonezawa
authors: Satohiro
authors: S
authors: Masuda
authors: Kazuo
authors: K
authors: Matsubara
authors: Keiko
authors: K
authors: Shimizu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006540:Herbicides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000166:cytology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D010269:Paraquat / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000071701:Regulatory Factor X Transcription Factors; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D006540:Herbicides; C501005:MT-ATP6 protein, human; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D053148:Caspase 3; D025261:Mitochondrial Proton-Translocating ATPases; D010269:Paraquat