Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1502, Issue 3, Pages 481-494Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0925-4439(00)00071-5
Keywords
glycation; NO synthase activity; epithelial cell; kidney
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Nitric oxide (NO) is important in the regulation of renal tubular function. We have investigated whether glycated proteins could impair the NO production by examining the effects of Amadori products (AP-BSA) and advanced glycation end products (AGE-BSA) on primary cultures of rabbit proximal tubular epithelial (PTE) cells. Nitric oxide synthase activity was assessed by measurement of the conversion of L-arginine to L-citrulline and by production of NO, after short-term (30 min) or long-term (1 or 3 days) incubation. Short incubations of PTE cells with either 200 mug/ml AP-BSA or 40 mug/ml ACE-BSA significantly decreased NO production. AP-BSA (3000 mug/ml) inhibited the Ca2+-dependent NOS activity even though above 50 mug/ml it increased Ca2+-independent NOS activity. In contrast, 40 mug/ml AGE-BSA inhibited both isoforms of NOS. Longer incubations with 200 mug/ml AP-BSA or 250 mug/ml AGE-BSA decreased NO release and inhibited Ca2+-dependent and -independent NOS activities. APs did not affect NO release by S-nitroso-N-acetyl-penicillamine (SNAP), while 250 mug/ml AGEs decreased it. After 3 days incubation, glycation products had no effect on the NOS cell content. Cell viability and proliferation were not modified under these experimental conditions, suggesting that the fall in NO production was not due to there being fewer cells. These data indicate that APs and AGEs directly inhibit NOS activity, and additionally that AGEs quench released NO. Thus, both types of glycated proteins alter the production of NO by PTE cells and could participate in the renal tubule dysfunction associated with aging and diabetes. (C) 2000 Elsevier Science B.V. All rights reserved.
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