Sodium tauroursodeoxycholate prevents paraquat-induced cell death by suppressing endoplasmic reticulum stress responses in human lung epithelial A549 cells

• Published in: Biochemical and biophysical research communications 2013-03, Vol.432 (4), p.689-694
• Main Authors: Omura, Tomohiro, Asari, Masaru, Yamamoto, Joe, Oka, Kumiko, Hoshina, Chisato, Maseda, Chikatoshi, Awaya, Toshio, Tasaki, Yoshikazu, Shiono, Hiroshi, Yonezawa, Atsushi, Masuda, Satohiro, Matsubara, Kazuo, Shimizu, Keiko
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Caspase 3 - biosynthesis; Cell Line; Chemical chaperone; DNA-Binding Proteins - metabolism; Endoplasmic reticulum stress (ERS); Endoplasmic Reticulum Stress - drug effects; Enzyme Activation - drug effects; Eukaryotic Initiation Factor-2 - metabolism; Herbicides - antagonists & inhibitors; Herbicides - toxicity; Humans; Lung - cytology; Mitochondrial Proton-Translocating ATPases - metabolism; Paraquat; Paraquat - antagonists & inhibitors; Paraquat - toxicity; Regulatory Factor X Transcription Factors; Respiratory Mucosa - cytology; Respiratory Mucosa - drug effects; Respiratory Mucosa - enzymology; Sodium tauroursodeoxycholate (TUDCA); Taurochenodeoxycholic Acid - pharmacology; Transcription Factors - metabolism; Unfolded protein response (UPR); Unfolded Protein Response - drug effects
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.01.131

► ER stress (ERS) response is involved in the pathogenesis of paraquat poisoning. ► Parkin may be a useful index of paraquat poisoning. ► TUDCA, a chemical chaperone, inhibits paraquat-induced ERS response. ► TUDCA suppresses caspase-3 activation and cell death caused by paraquat. ► TUDCA represents a potential therapy for paraquat poisoning and pulmonary fibrosis. 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.