The von Hippel-Lindau Gene Product Inhibits Renal Cell Apoptosis via Bcl-2-dependent Pathways

Prasad Devarajan, Maryely De Leon, Farahnaz Talasazan, Alan R. Schoenfeld, Eliot J. Davidowitz, Robert D. Burk

Research output: Contribution to journalArticle

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Abstract

Previous studies have reported a protective role for the von Hippel-Lindau (VHL) gene products against proapoptotic cellular stresses, but the mechanisms remain unclear. In this study, we examined the role of VHL in renal cells subjected to chemical hypoxia, using four VHL-negative and two VHL-positive cell lines. VHL-negative renal carcinoma cells underwent apoptosis following chemical hypoxia (short-term glucose deprivation and antimycin treatment), as evidenced by morphologic changes and internucleosomal DNA cleavage. Reintroduction of VHL expression prevented this apoptosis. VHL-negative cells displayed a significant (greater than 5-fold) activation of caspase 9 and release of cytochrome c into the cytosol following chemical hypoxia. In contrast, VHL-positive cells showed minimal caspase 9 activation, and absence of cytochrome c release under the same conditions. Caspase 8 was only minimally activated in both VHL-negative and -positive cells. In addition, VHL-positive cells displayed a striking up-regulation of Bcl-2 expression (5-fold) following chemical hypoxia. Antisense oligonucleotides to Bcl-2 significantly down-regulated Bcl-2 protein expression in VHL-positive cells and rendered them sensitive to apoptosis. Overexpression of Bcl-2 in VHL-negative cells conferred resistance to apoptosis. Our results suggest that VHL protects renal cells from apoptosis via Bcl-2-dependent pathways.

Original languageEnglish (US)
Pages (from-to)40599-40605
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number44
DOIs
StatePublished - Nov 2 2001

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Genes
Cells
Apoptosis
Kidney
Caspase 9
Cytochromes c
Chemical activation
Caspase 8
Antisense Oligonucleotides
DNA Cleavage
Renal Cell Carcinoma
Cytosol
Glucose
Up-Regulation
DNA
Cell Line
Hypoxia
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

The von Hippel-Lindau Gene Product Inhibits Renal Cell Apoptosis via Bcl-2-dependent Pathways. / Devarajan, Prasad; De Leon, Maryely; Talasazan, Farahnaz; Schoenfeld, Alan R.; Davidowitz, Eliot J.; Burk, Robert D.

In: Journal of Biological Chemistry, Vol. 276, No. 44, 02.11.2001, p. 40599-40605.

Research output: Contribution to journalArticle

Devarajan, P, De Leon, M, Talasazan, F, Schoenfeld, AR, Davidowitz, EJ & Burk, RD 2001, 'The von Hippel-Lindau Gene Product Inhibits Renal Cell Apoptosis via Bcl-2-dependent Pathways', Journal of Biological Chemistry, vol. 276, no. 44, pp. 40599-40605. https://doi.org/10.1074/jbc.M103424200
Devarajan, Prasad ; De Leon, Maryely ; Talasazan, Farahnaz ; Schoenfeld, Alan R. ; Davidowitz, Eliot J. ; Burk, Robert D. / The von Hippel-Lindau Gene Product Inhibits Renal Cell Apoptosis via Bcl-2-dependent Pathways. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 44. pp. 40599-40605.
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