AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury

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Ying Wang1, Zhiwen Liu1, Shaoqun Shu1

  • 1Department of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China.

Frontiers in Physiology
|January 4, 2021
PubMed

Insights

Autophagy protects kidney cells from cisplatin damage by clearing cellular waste. Targeting key regulators, mammalian target of rapamycin (mTOR) and adenosine-monophosphate activated-protein kinase (AMPK), may prevent acute kidney injury.

Area of Science:

  • Cellular Biology
  • Renal Physiology
  • Molecular Medicine

Background:

  • Autophagy is a vital cellular process for maintaining homeostasis by degrading and recycling damaged components.
  • Mammalian target of rapamycin (mTOR) and adenosine-monophosphate activated-protein kinase (AMPK) are critical regulators of autophagy.
  • Cisplatin chemotherapy can induce acute kidney injury (AKI), a significant clinical concern.

Purpose of the Study:

  • To investigate the role of autophagy in cisplatin-induced AKI.
  • To explore the involvement of mTOR and AMPK in regulating autophagy during AKI.
  • To assess the potential of targeting mTOR and AMPK for kidney protection in AKI.

Main Methods:

  • Utilized models of cisplatin-induced AKI.
  • Examined autophagy induction in renal tubular epithelial cells.
  • Assessed the activity and role of mTOR and AMPK signaling pathways.

Main Results:

  • Autophagy is rapidly induced in renal tubular epithelial cells following cisplatin exposure.
  • Both mTOR and AMPK play significant roles in modulating autophagy during cisplatin-induced AKI.
  • The modulation of autophagy via mTOR and AMPK pathways is linked to cell survival in AKI.

Conclusions:

  • Autophagy acts as a cytoprotective mechanism against cisplatin-induced nephrotoxicity.
  • mTOR and AMPK are key regulators of this protective autophagy in AKI.
  • Targeting mTOR and/or AMPK presents a promising therapeutic strategy for preventing cisplatin-mediated kidney damage.
Keywords:
AMPKacute kidney injuryautophagycisplatinmTORnephrotoxicity

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