Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells

Sudharsan Periyasamy-Thandavan, Man Jiang, Qingqing Wei, Robert Smith, Xiao-Ming Yin, Zheng Dong

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

Autophagy is a cellular process of bulk degradation of damaged organelles, protein aggregates and other macromolecules in the cytoplasm. It is thought to be a general response to stress contributing to cell death; alternatively it might act as a cytoprotective mechanism. Here we found that administration of cisplatin induced the formation of autophagic vesicles and autophagosomes in mouse kidneys. In cultured proximal tubular cells, the nephrotoxin caused autophagy in a dose- and time-dependent manner prior to apoptosis. Notably, autophagy occurred within hours of cisplatin administration but this was partially suppressed by the p53 inhibitor pifithrin-α, suggesting that p53 is involved in autophagic signaling. This cisplatin-induced autophagy was attenuated in renal cells stably transfected with Bcl-2, suggesting an anti-autophagic role for this well-known anti-apoptotic protein. Blockade of autophagy with pharmacological inhibitors (3-methyladenine or bafilomycin) or shRNA knockdown of the autophagic gene Beclin increased tubular cell apoptosis during cisplatin treatment. Our study has found that autophagy occurs in acute kidney injury and this may be an important protective mechanism for cell survival.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalKidney International
Volume74
Issue number5
DOIs
StatePublished - Sep 2008
Externally publishedYes

Fingerprint

Autophagy
Cisplatin
Kidney
Wounds and Injuries
Apoptosis
Gene Knockdown Techniques
Apoptosis Regulatory Proteins
Acute Kidney Injury
Organelles
Small Interfering RNA
Cell Survival
Cytoplasm
Cell Death
Pharmacology

Keywords

  • Acute kidney injury
  • Apoptosis
  • Autophagy
  • Bcl-2
  • Cisplatin
  • p53

ASJC Scopus subject areas

  • Nephrology

Cite this

Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells. / Periyasamy-Thandavan, Sudharsan; Jiang, Man; Wei, Qingqing; Smith, Robert; Yin, Xiao-Ming; Dong, Zheng.

In: Kidney International, Vol. 74, No. 5, 09.2008, p. 631-640.

Research output: Contribution to journalArticle

Periyasamy-Thandavan, S, Jiang, M, Wei, Q, Smith, R, Yin, X-M & Dong, Z 2008, 'Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells', Kidney International, vol. 74, no. 5, pp. 631-640. https://doi.org/10.1038/ki.2008.214
Periyasamy-Thandavan, Sudharsan ; Jiang, Man ; Wei, Qingqing ; Smith, Robert ; Yin, Xiao-Ming ; Dong, Zheng. / Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells. In: Kidney International. 2008 ; Vol. 74, No. 5. pp. 631-640.
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