Abstract
The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10-7 mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10-8 mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
| Original language | English |
|---|---|
| Pages (from-to) | 478-490 |
| Number of pages | 13 |
| Journal | Apoptosis |
| Volume | 16 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2011 May 1 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmaceutical Science
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Cancer Research
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Local kallikrein-kinin system is involved in podocyte apoptosis under diabetic conditions. / Kwak, Seung Jae; Paeng, Jisun; Kim, Do Hee; Lee, Sun Ha; Nam, Bo Young; Kang, Hye Young; Li, Jin Ji; Jung, Dong Sub; Han, SeungHyeok; Ryu, Dong Ryeol; Park, Jung Tak; Chang, Tae Ik; Yoo, TaeHyun; Han, Dae Suk; Kang, Shin-Wook.
In: Apoptosis, Vol. 16, No. 5, 01.05.2011, p. 478-490.Research output: Contribution to journal › Article
TY - JOUR
T1 - Local kallikrein-kinin system is involved in podocyte apoptosis under diabetic conditions
AU - Kwak, Seung Jae
AU - Paeng, Jisun
AU - Kim, Do Hee
AU - Lee, Sun Ha
AU - Nam, Bo Young
AU - Kang, Hye Young
AU - Li, Jin Ji
AU - Jung, Dong Sub
AU - Han, SeungHyeok
AU - Ryu, Dong Ryeol
AU - Park, Jung Tak
AU - Chang, Tae Ik
AU - Yoo, TaeHyun
AU - Han, Dae Suk
AU - Kang, Shin-Wook
PY - 2011/5/1
Y1 - 2011/5/1
N2 - The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10-7 mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10-8 mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
AB - The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10-7 mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10-8 mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
UR - http://www.scopus.com/inward/record.url?scp=79955856377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955856377&partnerID=8YFLogxK
U2 - 10.1007/s10495-011-0585-1
DO - 10.1007/s10495-011-0585-1
M3 - Article
C2 - 21373934
AN - SCOPUS:79955856377
VL - 16
SP - 478
EP - 490
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
SN - 1360-8185
IS - 5
ER -