NO DECREASES PHOSPHORYLATION OF FOCAL ADHESION PROTEINS VIA REDUCTIONOF CA IN RAT AORTIC SMOOTH-MUSCLE CELLS

Citation
K. Kaur et al., NO DECREASES PHOSPHORYLATION OF FOCAL ADHESION PROTEINS VIA REDUCTIONOF CA IN RAT AORTIC SMOOTH-MUSCLE CELLS, American journal of physiology. Heart and circulatory physiology, 43(5), 1998, pp. 1613-1619
Citations number
31
Categorie Soggetti
Physiology
ISSN journal
03636135
Volume
43
Issue
5
Year of publication
1998
Pages
1613 - 1619
Database
ISI
SICI code
0363-6135(1998)43:5<1613:NDPOFA>2.0.ZU;2-E
Abstract
Our laboratory has previously reported that the antimitogenic effect o f nitric oxide (NO) in primary cultures of rat aortic smooth muscle ce lls may be attributed to activation of protein tyrosine phosphatase an d dephosphorylation of protein phosphotyrosine [G. S. Dhaunsi, C. Matt hews, K. Kaur, and A. Hassid. Am. J. Physiol. 272 (Heart Circ. Physiol . 41): H1342-H1349, 1997]. The goal of the current study was to invest igate the role of cytoplasmic Ca in this process and to identify prote in substrates that are dephosphorylated by treatment with NO. Treatmen t of primary rat aortic smooth muscle cell cultures with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) decreased cytoplasmic Ca levels and elicited phosphotyrosine dephosphorylation. Both effects were mim icked by the extracellular and intracellular Ca chelators ethylene gly col-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and , 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), respec tively, and by the Ca channel blocker nifedipine. Conversely, elevatio n of cytoplasmic Ca via the use of the Ca ionophore A-23187 or high ex tracellular K+ prevented or attenuated SNAP-induced dephosphorylation. Both BAPTA and nifedipine also decreased DNA synthesis, providing fur ther evidence to link dephosphorylation to antipitogenesis. Two of the proteins dephosphorylated by treatment of cells with NO or EGTA were identified as the focal adhesion proteins, cortactin and paxillin. The se results indicate that NO-induced dephosphorylation of protein phosp hotyrosine is mediated by reduction of cytoplasmic Ca and suggest that dephosphorylation of focal adhesion proteins may be of relevance to t he antimitogenic effect of NO.