Regulation of Angiotensin II Binding in Renal Proximal Tubule Cells by High Glucose : I.Involvement of PKC, Ca2+, and Oxidative Stress.
- Author:
Soo Hyun PARK
1
;
Ho Jae HAN
Author Information
1. Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea. hjhan@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
Angiotensin II receptor;
Glucose;
Kidney;
Ca2+;
Oxidative stress;
Protein kinase C
- From:Korean Journal of Nephrology
2001;20(5):759-767
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Renin-angiotensin system is associated with development of diabetic nephropathy. However, its mechanism was not elucidated, although downregulation of angiotensin II(ANG II) receptor was evident in kidney under diabetic condition. Thus, we investigated the involvement of PKC, Ca2+, and oxidative stress on high glucose-induced inhibition of ANG II receptor in the primary cultured renal proximal tubule cells. 25 mM glucose, but not mannitol and L-glucose, inhibited ANG II binding. 25 mM glucose-induced inhibition of ANG II binding was blocked by taurine, N-acetylcystein, vitamin E, suggesting the role of oxidative stress. 25 mM glucose-induced increase of lipid peroxide(LPO) and inhibition of ANG II binding was prevented by nifedifine and methoxyverapamil, L type Ca2+ channel blockers, suggesting the role of extracellular Ca2+. Indeed, high glucose-induced inhibition of ANG II binding was also blocked by H-7 and TPA pretreatment and high glucose-induced increase of Ca2+ uptake was prevented by PKC inhibitor and TPA pretreatment. In addition, inhibition of ANG II binding by high glucose was blocked by these agents. In conclusion, high glucose, in part, inhibits ANG II binding via PKC-Ca2+-oxidative stress signal cascade in the PTCs.
