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J Biol Chem. 2000 Apr 21;275(16):12223-30.

Distinct effects of N-acetylcysteine and nitric oxide on angiotensin II-induced epidermal growth factor receptor phosphorylation and intracellular Ca(2+) levels.

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  • 1Department of Biochemistry and Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.


These studies describe inhibitory effects of N-acetylcysteine on several biochemical events associated with the activation of extracellular signal-regulated kinases (ERK) by angiotensin II in the cardiac fibroblast and compare these effects with those of the nitric oxide donor, S-nitroso-N-acetylpenicillamine, an agent we showed previously to inhibit angiotensin II-induced ERK activation and the concomitant phosphorylation of proline-rich tyrosine kinase 2 (Wang, D., Yu, X., and Brecher, P. (1999) J. Biol. Chem. 274, 24342-24348). The transactivation of the epidermal growth factor receptor by angiotensin II, a process required for the activation of ERK, was inhibited by N-acetylcysteine but not by nitric oxide. The transactivation of the epidermal growth factor receptor by angiotensin II was shown to be independent of intracellular calcium increases. Nitric oxide, but not N-acetylcysteine, inhibited the angiotensin II-induced increase in intracellular Ca(2+). Neither nitric oxide nor N-acetylcysteine inhibited either phospholipase C activation or inositol triphosphate generation in response to angiotensin II. N-Acetylcysteine did inhibit the phosphorylation of the calcium sensitive tyrosine kinases PYK2 and Src, effects that also occurred using nitric oxide. These studies describe a novel effect of N-acetylcysteine on cross-talk between a G protein-linked receptor and a tyrosine kinase receptor and offer additional molecular insight to explain how N-acetylcysteine and nitric oxide act at different sites and might have an additive effect on specific hormonal responses.

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