mTOR 促进肾小管细胞内质网应激和相关凋亡。
mTOR contributes to ER stress and associated apoptosis in renal tubular cells.
机构信息
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;
出版信息
Am J Physiol Renal Physiol. 2015 Feb 1;308(3):F267-74. doi: 10.1152/ajprenal.00629.2014. Epub 2014 Nov 26.
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.
内质网应激与急性和慢性肾脏疾病的发病机制有关。然而，内质网应激在肾脏细胞和组织中的分子调控仍知之甚少。在这项研究中，我们研究了衣霉素诱导的肾近端小管细胞（RPTC）内质网应激。衣霉素在 2 小时内诱导 RPTC 中 PERK 和 eIF2α 的磷酸化和激活，随后诱导 GRP78 和 CHOP。一致地，衣霉素也诱导 RPTC 凋亡。有趣的是，mTOR 在衣霉素处理过程中迅速被激活，这表明 mTOR 和 p70S6K 的磷酸化。用雷帕霉素抑制 mTOR 可部分抑制衣霉素处理过程中 PERK 和 eIF2a 的磷酸化以及 CHOP 和 GRP78 的诱导。雷帕霉素也抑制衣霉素处理过程中的细胞凋亡并增加细胞存活率。总之，结果表明 mTOR 在 ER 应激中发挥调节作用，抑制 mTOR 可能对 ER 应激相关肾脏疾病具有潜在的治疗作用。
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