1. ¹Department of Internal Medicine, College of Medicine, Kwandong University, Goyang, Gyeonggi-Do, Korea
2. ²Department of Internal Medicine, College of Medicine, Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea
3. ³Nephrology and Dialysis Unit, Department of Internal Medicine, The Affiliated Hospital, YanBian University Medical College, JiLin, China
4. ⁴Department of Anatomy and Neurobiology, College of Medicine, Gyeongsang National University, Gyeongnam, Korea
5. ⁵Department of Internal Medicine, College of Medicine, Gyeongsang National University, Gyeongnam, Korea

Correspondence: Shin-Wook Kang, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul 120-752, Korea. E-mail: kswkidney@yumc.yonsei.ac.kr

⁶These authors contributed equally to this work.

Received 17 September 2008; Revised 22 April 2009; Accepted 2 June 2009; Published online 5 August 2009.

Abstract

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.