The relationship between high glucose-induced secretion of IGFs and PKC or oxidative stress in mesangial cells |
Su-hyun Park1, Jung-sun Heo1, Chang-won Kang2, Ho-jae Han1 |
1Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University 2Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University |
Mesangial 세포에서 고포도당에 의한 IGFs 분비와 PKC 및 산화성 스트레스와의 관련성에 관한 연구 |
박수현1, 허정선1, 강창원2, 한호재1 |
1전남대학교 수의과대학 생리학교실 2전북대학교 수의과대학 생리학교실, 생체안전성 연구소 |
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Abstract |
The proliferation of mesangial cells has been associated with the development of diabetic nephropathy. The cell proliferation has been regulated by diverse growth factors. Among them, insulin like growth factors(IGFs) are also involved in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion and the relationship between high glucose-induced secretion of IGFs and PKC or oxidative stress in the mesangial cells. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. High glucose(25 mM) increased IGF-I and IGF-II secretion. High glucose-induced increase of IGF-I and IGF-II secretion were blocked by taurine($2{ imes}10^{-3}$ M), N-acetyl cystein(NAC, $10^{-5}M$), or GSH($10^{-5}M$) (antioxidants), suggesting the role of oxidative stress. High glucose-induced secretion of IGF-I and IGF-II were blocked by H-7, staurosporine, and bisindolylmaleimide I(protein kinase C inhibitors). On the other hand, high glucose also increased lipid peroxide (LPO) formation in a dose dependent manner. In addition, high glucoseinduced stimulation of LPO formation was blocked by PKC inhibitors. These results suggest that PKC is responsible for the increase of oxidative stress in the action of high glucose-induced secretion of IGF-I and IGF-II in mesangial cells. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via PKCoxidative stress signal pathways in mesangial cells. |
Key Words:
Insulin-like growth factors, high glucose, PKC, oxidative stress, mesangial cell, kidney |
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