Journal
KIDNEY INTERNATIONAL
Volume 76, Issue 8, Pages 838-848Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2009.286
Keywords
apoptosis; diabetic nephropathy; heme oxygenase-1; high glucose; podocyte
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Funding
- Medical Sciences, Yonsei University [BK21]
- Korean government [R01-2007-000-20263-0, R13-2002-054-04001-0]
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Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose-treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose-treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions. Kidney International (2009) 76, 838-848; doi:10.1038/ki.2009.286; published online 5 August 2009
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