Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

被引:70
作者
Lee, Sang Choel [2 ]
Han, Seung Hyeok [1 ]
Li, Jin Ji [1 ,3 ]
Lee, Sun Ha [1 ]
Jung, Dong-Sub [1 ]
Kwak, Seung-Jae [1 ]
Kim, Seung Hye [1 ]
Kim, Dong Ki [1 ]
Yoo, Tae-Hyun [1 ]
Kim, Jin Hyun [4 ]
Chang, Se-Ho [5 ]
Han, Dae Suk [1 ]
Kang, Shin-Wook [1 ]
机构
[1] Yonsei Univ, Coll Med, Dept Internal Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea
[2] Kwandong Univ, Coll Med, Dept Internal Med, Goyang, Gyeonggi Do, South Korea
[3] YanBian Univ, Coll Med, Dept Internal Med, Affiliated Hosp,Nephrol & Dialysis Unit, Yanji, Jilin, Peoples R China
[4] Gyeongsang Natl Univ, Coll Med, Dept Anat & Neurobiol, Gyeongnam, South Korea
[5] Gyeongsang Natl Univ, Coll Med, Dept Internal Med, Gyeongnam, South Korea
关键词
apoptosis; diabetic nephropathy; heme oxygenase-1; high glucose; podocyte; RENAL INJURY; DIFFERENTIAL EXPRESSION; OXIDATIVE STRESS; MESSENGER-RNA; GROWTH-FACTOR; KIDNEY; GENE; ISCHEMIA; REPERFUSION; PATHWAYS;
D O I
10.1038/ki.2009.286
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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
引用
收藏
页码:838 / 848
页数:11
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