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Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

Cyclosporine A induces senescence in renal tubular epithelial cells

Paul Jennings1, Christian Koppelstaetter, Sonia Aydin

  • 1Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria.

American Journal of Physiology. Renal Physiology
|June 29, 2007
PubMed

Insights

Cyclosporine A (CsA) induces cellular senescence in human kidney tubule cells by increasing oxidative stress. Scavenging reactive oxygen species can prevent this CsA-induced senescence, offering potential therapeutic avenues.

Area of Science:

  • Nephrology
  • Cell Biology
  • Toxicology

Background:

  • Cyclosporine A (CsA) is a vital immunosuppressant with known nephrotoxic effects.
  • The precise mechanisms underlying CsA-induced renal tubular toxicity remain unclear.
  • Shared features between CsA nephropathy and kidney aging suggest a role for cellular senescence.

Purpose of the Study:

  • To investigate whether CsA induces a stress-induced senescent phenotype in renal tubular cells.
  • To elucidate the role of reactive oxygen species (ROS) in CsA-mediated cellular senescence.
  • To explore potential interventions for CsA-induced nephrotoxicity.

Main Methods:

  • In vitro studies using HK-2 cells and primary human proximal tubular cells.
  • Assessment of CsA effects on hydrogen peroxide (H2O2) production, cell cycle progression, and DNA synthesis.
  • Analysis of telomere length, p53 phosphorylation, and expression of senescence markers (p21, p16).
  • Evaluation of the impact of catalase (ROS scavenger) on CsA-treated cells.

Main Results:

  • CsA induced H2O2 production, G0/G1 cell cycle arrest, and inhibited DNA synthesis.
  • CsA exposure led to telomere shortening, increased p53 phosphorylation, and elevated p21(Kip1) mRNA.
  • Primary proximal tubular cells showed increased p16(INK4a) expression after prolonged CsA exposure.
  • Catalase treatment prevented telomere shortening and partially restored DNA synthesis in CsA-exposed cells.

Conclusions:

  • CsA induces cellular senescence in human renal tubular epithelial cells.
  • Oxidative stress plays a critical role in CsA-induced senescence.
  • Targeting ROS may offer a strategy to mitigate CsA nephrotoxicity.

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