The pathological role of Bax in cisplatin nephrotoxicity

QingQing Wei, G. Dong, J. Franklin, Zheng Dong

Research output: Contribution to journalArticle

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Abstract

Nephrotoxicity induced by cisplatin involves tubular cell necrosis and apoptosis; the latter of which may be initiated by multiple mechanisms including activation of the intrinsic mitochondrial pathway. In cultured tubular epithelial cells, cisplatin can activate the proapoptotic protein Bax resulting in cytochrome c release, caspase activation, and apoptosis. Definitive evidence for the involvement of Bax in cisplatin nephrotoxicity in vivo, however, is lacking. We analyzed Bax regulation during cisplatin nephrotoxicity in wild-type mice and determined the pathological role of Bax using mice in which this gene was knocked out. In wild-type mice, cisplatin induced Bax in renal tubular cells which became active, accumulated in the mitochondria, and was accompanied by acute kidney injury. Compared with the wild-type mice renal function, as measured by blood urea nitrogen and serum creatinine, was partially but significantly preserved in Bax knockout mice. The number of apoptotic cells was decreased as was general tissue damage. Additionally, cisplatin-induced cytochrome c release was attenuated in the Bax-deficient mice. This significant decrease in apoptosis and in cytochrome c release was also mirrored in primary cultures of proximal tubular cells prepared from Bax knockout animals. Collectively, our results provide compelling evidence for a role of Bax and its related apoptotic pathway in cisplatin nephrotoxicity.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalKidney International
Volume72
Issue number1
DOIs
StatePublished - Jul 1 2007

Fingerprint

Cisplatin
Cytochromes c
Apoptosis
Kidney
bcl-2-Associated X Protein
Blood Urea Nitrogen
Caspases
Acute Kidney Injury
Knockout Mice
Creatinine
Mitochondria
Necrosis
Cell Count
Epithelial Cells
Serum
Genes

Keywords

  • Acute kidney injury
  • Apoptosis
  • Bax
  • Cisplatin nephrotoxicity
  • Cytochrome c
  • Mitochondria

ASJC Scopus subject areas

  • Nephrology

Cite this

The pathological role of Bax in cisplatin nephrotoxicity. / Wei, QingQing; Dong, G.; Franklin, J.; Dong, Zheng.

In: Kidney International, Vol. 72, No. 1, 01.07.2007, p. 53-62.

Research output: Contribution to journalArticle

Wei, QingQing ; Dong, G. ; Franklin, J. ; Dong, Zheng. / The pathological role of Bax in cisplatin nephrotoxicity. In: Kidney International. 2007 ; Vol. 72, No. 1. pp. 53-62.
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