Negative feedback loop of autophagy and endoplasmic reticulum stress in rapamycin protection against renal ischemia-reperfusion injury during initial reperfusion phase

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Xinyuan LiJie Li

Abstract

Rapamycin, an immunosuppressant, is widely used in patients with kidney transplant. However, the therapeutic effects of rapamycin remain controversial. Additionally, previous studies have revealed deleterious effects of rapamycin predominantly when administered for ≥24 h. Few studies, however, have focused on the short-term effects of rapamycin administered only during the initial reperfusion phase. As such, we designed this study to explore the potential effects and mechanisms of rapamycin under a specific therapeutic regimen in which rapamycin is mixed in the perfusate during the initial reperfusion phase (within 24 h). Interestingly, we found that rapamycin maintained renal function and attenuated ischemia-reperfusion (I/R)-induced apoptosis in vivo and in vitro during the initial reperfusion phase, especially at 8 h after reperfusion. Simultaneously, rapamycin activated autophagy and inhibited endoplasmic reticulum (ER) stress and 3 pathways of unfolding protein response: ATF6, PERK, and IRE1α. Interestingly, we further found that the protective effects of rapamycin were suppressed when autophagy was inhibited by chloroquine and 3-methyladenine or when ER stress was induced by thapsigargin. Moreover, in terms of the regulat...Continue Reading

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Citations

Aug 20, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Murat KabaklıoğluRecep Eröz
Jan 23, 2021·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Omnia S ErfanMarwa Abd El-Kader

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