Cellular control of nitric oxide synthase expression and activity in rat cardiomyocytes

Item Type:	Article
Title:	Cellular control of nitric oxide synthase expression and activity in rat cardiomyocytes
Creators Name:	Slezak, J. and Buchwalow, I.B. and Schulze, W. and Karczewski, P. and Wallukat, G. and Samoilova, V.E. and Krause, E.G. and Neumann, J. and Haller, H.
Abstract:	Potential ortho- and pathophysiological roles for nitric oxide synthases (NOS) in cardiac functions have been and are continuing to be described. However, cellular signaling mechanisms controlling nitric oxide (NO) production in the heart remain obscure. The aim of this study was to investigate signaling mechanisms involved in regulation of NOS expression and NO generation in cardiomyocytes. Using immunocytochemical methods in conjunction with western blotting, we have found that cultured neonatal rat cardiomyocytes express constitutively all three NOS isoforms targeted predominantly to the particulate component of cardiomyocytes-mitochondria and along contractile fibers, as well as along plasma membrane including T-tubules. Biochemical assay of NO generation has shown that exposure of cultured neonatal rat cardiac cells to isoproterenol (β-adrenergic stimulation), iloprost [stable prostaglandin I2 (PGI2) analogue], as well as inflammatory cytokines and dibutyryl adenosine-3′,5′-monophosphate (db-cAMP), resulted in a marked up-regulation of NOS expression by cardiomyocytes. In db-cAMP-stimulated cells, inhibition of protein kinase A (PKA) and protein kinase C (PKC) reduced immunolabeling of NOS and concomitantly lowered NO production. Taken together, these data point to an involvement of β-adrenergic mechanisms, cytokine and PGI2 receptors, adenylyl cyclase, PKA, and PKC in the control of NO generation and expression of NOS in rat cardiomyocytes.
Keywords:	Bucladesine, Cardiac Myocytes, Cultured Cells, Enzymologic Gene Expression Regulation, Isoenzymes, Newborn Animals, Nitric Oxide, Nitric Oxide Synthase, Nitrites, Protein Kinase Inhibitors, Tetradecanoylphorbol Acetate, Animals, Rats
Source:	Antioxidants and Redox Signaling
ISSN:	1523-0864
Publisher:	Mary Ann Liebert
Volume:	6
Number:	2
Page Range:	345-352
Date:	1 April 2004
Official Publication:	https://doi.org/10.1089/152308604322899413
PubMed:	View item in PubMed

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