title: mTOR contributes to ER stress and associated apoptosis in renal tubular cells.
abstract: ER stress has been implicated in the pathogenesis of both acute and chronic kidney diseases. However, the molecular regulation of ER stress in kidney cells and tissues remains poorly understood. In this study, we examined tunicamycin-induced ER stress in renal proximal tubular cells (RPTC). Tunicamycin induced the phosphorylation and activation of PERK and eIF2α within 2 h in RPTC, which was followed by the induction of GRP78 and CHOP. Consistently, tunicamycin also induced apoptosis in RPTC. Interestingly, mTOR was activated rapidly during tunicamycin treatment, as indicated by phosphorylation of both mTOR and p70S6K. Inhibition of mTOR with rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during tunicamycin treatment. Rapamycin also inhibited apoptosis during tunicamycin treatment and increased cell survival. Collectively, the results suggest that mTOR plays a regulatory role in ER stress, and inhibition of mTOR may have potential therapeutic effects in ER stress-related renal diseases.
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Reagents University and Charlie Norwood Veterans Affairs (VA) Medical Center, Augusta, Georgia;
authors.forename: Guie
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Reagents University and Charlie Norwood VA Medical Center, Augusta, Georgia; and.
authors.forename: Shuang
authors.initials: S
authors.lastname: Huang
authors.affiliation: Cancer Center, Georgia Reagents University and Charlie Norwood VA Medical Center, Augusta, Georgia.
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Ding
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Reagents University and Charlie Norwood Veterans Affairs (VA) Medical Center, Augusta, Georgia; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; zdong@gru.edu.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D015852:Eukaryotic Initiation Factor-2; D014415:Tunicamycin; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: apoptosis; endoplasmic reticulum stress; mammmalian target of rapamycin; renal tubular cells; tunicamycin