title: ER stress inducer, thapsigargin, decreases extracellular-superoxide dismutase through MEK/ERK signalling cascades in COS7 cells.
abstract: It has been reported that tubular cells suffer an endoplasmic reticulum (ER) stress during the development of chronic kidney disease, which is a potent risk factor of cardiovascular disease. Moreover, under these conditions, reactive oxygen species are generated and induce cell injury. Extracellular-superoxide dismutase (EC-SOD) is a member of SODs and protects the cells from oxidative stress. Here, it is demonstrated that thapsigargin, an ER stress inducer, decreased EC-SOD expression, whereas the expression of Cu,Zn-SOD and Mn-SOD was not changed. On the other hand, another ER stress inducer, tunicamycin, did not affect the expression of EC-SOD. Further, it was shown that thapsigargin has the ability to activate extracellular-signal regulated kinase (ERK), but tunicamycin does not. Moreover, pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK)/ERK, suppressed thapsigargin-triggered EC-SOD reduction, suggesting that MEK/ERK signalling should play an important role in the regulation of EC-SOD in COS7 cells under ER stress conditions.
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. tekamiya@gifu-pu.ac.jp
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.forename: Aya
authors.initials: A
authors.lastname: Obara
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
mesh_terms: D000818:Animals; D019556:COS Cells; D015687:Cell Hypoxia; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D013312:Stress, Physiological; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D019284:Thapsigargin; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases