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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Activation and involvement of p53 in cisplatin-induced nephrotoxicity

Qingqing Wei1, Guie Dong, Tianxin Yang

  • 1Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912, USA.

American Journal of Physiology. Renal Physiology
|August 3, 2007
PubMed

Insights

The tumor suppressor protein p53 plays a key role in acute kidney injury caused by the chemotherapy drug cisplatin. Inhibiting or removing p53 protects against cisplatin nephrotoxicity.

Area of Science:

  • Nephrology
  • Oncology
  • Molecular Biology

Background:

  • Cisplatin is a vital chemotherapy agent, but its use is restricted by severe acute kidney injury (AKI).
  • The precise molecular pathways driving cisplatin-induced nephrotoxicity remain largely unknown.
  • The tumor suppressor protein p53 is implicated in cellular stress responses, but its specific role in cisplatin AKI is unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism of cisplatin-induced nephrotoxicity.
  • To investigate the pathological role of p53 in cisplatin-induced kidney injury.

Main Methods:

  • Utilized pharmacological inhibition of p53 with pifithrin-alpha.
  • Employed p53 gene knockout mouse models.
  • Assessed kidney function, tissue damage, and apoptosis in wild-type and p53-deficient mice following cisplatin treatment.

Main Results:

  • Cisplatin treatment increased p53 phosphorylation and accumulation in mouse kidneys, correlating with AKI development.
  • Pifithrin-alpha mitigated cisplatin-induced kidney injury by suppressing p53 activation.
  • p53-deficient mice exhibited significantly reduced cisplatin nephrotoxicity, including better renal function, less tissue damage, and fewer apoptotic cells.

Conclusions:

  • The tumor suppressor protein p53 is a critical mediator of cisplatin-induced nephrotoxicity.
  • Targeting p53 activation may represent a therapeutic strategy to prevent or reduce cisplatin-induced kidney damage.
  • These findings highlight p53's involvement in cisplatin-induced renal cell apoptosis.

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