Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions.
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.
Lee
Sang Choel
SC
Department of Internal Medicine, Kwandong University, Goyang, Gyeonggi-Do, Korea.
Han
Seung Hyeok
SH
Li
Jin Ji
JJ
Lee
Sun Ha
SH
Jung
Dong-Sub
DS
Kwak
Seung-Jae
SJ
Kim
Seung Hye
SH
Kim
Dong Ki
DK
Yoo
Tae-Hyun
TH
Kim
Jin Hyun
JH
Chang
Se-Ho
SH
Han
Dae Suk
DS
Kang
Shin-Wook
SW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D004791:Enzyme Inhibitors; D051793:Hypoxia-Inducible Factor 1; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011524:Protoporphyrins; D051028:bcl-2-Associated X Protein; C017803:zinc protoporphyrin; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C491523:Hmox1 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D005947:Glucose