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KMID : 0648320100160010008
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Journal of The Korean Society of Hypertension
2010 Volume.16 No. 1 p.8 ~ p.17
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The Effect of Bradykinin on High-Glucose Induced Apoptosis in Cultured Podocytes
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Kwak Seung-Jae
Yoo Tae-Hyun
Kang Shin-Wook
Kim Kyung-Jin
Baek Doo-Hyun
Kim Woo-Shin
An Hye-Rim
Yu Min-A
Kim Seung-Jung
Kang Duk-Hee
Choi Kyu-Bok
Ryu Dong-Ryeol
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Abstract
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Background : In this study, we examined whether a local kallikrein-kinin system (KKS) exists in podocytes and whether expression of the components of the KKS and bradykinin (BK) production are changed in cultured podocytes exposed to high glucose medium. We also investigated the functional role of BK in podocyte apoptosis.
Methods : Immortalized mouse podocytes were cultured in media containing normal glucose (5.6 mM, NG), NG+24.4 mM mannitol (NG+M), and high glucose (30 mM, HG) with or without pretreatment with 10-8 M BK. BK levels were measured and mRNA and protein expression for all components of the KKS were evaluated. For assessment of apoptosis, western blots and Hoechst 33342 staining were done.
Results : In cultured podocytes exposed to HG medium compared to NG cells, we found decreases not only in kininogen, kallikrein, BK B1-receptor (B1R), and B2-receptor (B2R) mRNA and protein expression, but also in BK levels. Changes in expression of apoptosis-related molecules and in the number of apoptotic cells in HG-stimulated podocytes were significantly abrogated by BK treatment. BK also inhibited activation of the proapoptotic p38 mitogen-activated protein kinase induced by HG.
Conclusion : The expression of all components of the KKS is decreased in cultured podocytes exposed to HG. In addition, BK treatment ameliorates podocyte apoptosis. These findings suggest that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
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KEYWORD
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Podocyte, Apoptosis, Kallikrein-kinin system, Bradykinin
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