Expressional control of the `constitutive' isoforms of nitric oxide synthase (NOS I and NOS III)

^a Department of Pharmacology, Johannes Gutenberg University, D-55101 Mainz, Germany

Nitric oxide synthase (NOS) exists in three established isoforms. NOS I (NOS1, ncNOS) was originally discovered in neurons. This enzyme and splice variants thereof have since been found in many other cells and tissues. NOS II (NOS2, iNOS) was first identified in murine macrophages, but can also be induced in many other cell types. NOS III (NOS3, ecNOS) is expressed mainly in endothelial cells. Whereas NOS II is a transcriptionally regulated enzyme, NOS I and NOS III are considered constitutively expressed proteins. However, evidence generated in recent years indicates that these two isoforms are also subject to expressional regulation. In view of the important biological functions of these isoforms, changes in their expression may have physiological and pathophysiological consequences. This review recapitulates compounds and conditions that modulate the expression of NOS I and NOS III, summarizes transcriptional and posttranscriptional effects that underlie these changes, and—where known—describes the molecular mechanisms leading to changes in transcription, RNA stability, or translation of these enzymes.—Förstermann, U., Boissel, J.-P., Kleinert, H. Expressional control of the `constitutive' isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J. 12, 773–790 (1998)

Key Words: cellular expression • gene structure • transcription factors • transcriptional regulation • RNA stability • protein stability

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				M. Garcia-Duran, T. de Frutos, J. Diaz-Recasens, G. Garcia-Galvez, A. Jimenez, M. Monton, J. Farre, L. S. de Miguel, F. Gonzalez-Fernandez, M. d. M. Arriero, et al. Estrogen Stimulates Neuronal Nitric Oxide Synthase Protein Expression in Human Neutrophils Circ. Res., November 26, 1999; 85(11): 1020 - 1026. [Abstract] [Full Text] [PDF]

				T. Wallerath, K. Witte, S. C. Schafer, P. M. Schwarz, W. Prellwitz, P. Wohlfart, H. Kleinert, H.-A. Lehr, B. Lemmer, and U. Forstermann Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension PNAS, November 9, 1999; 96(23): 13357 - 13362. [Abstract] [Full Text] [PDF]

				K. D. Bloch Regulation of Endothelial NO Synthase mRNA Stability : RNA-Binding Proteins Crowd on the 3'-Untranslated Region Circ. Res., October 1, 1999; 85(7): 653 - 655. [Full Text] [PDF]

				E. Guillemard, B. Varano, F. Belardelli, A. M. Quero, and S. Gessani Inhibitory Activity of Constitutive Nitric Oxide on the Expression of Alpha/Beta Interferon Genes in Murine Peritoneal Macrophages J. Virol., September 1, 1999; 73(9): 7328 - 7333. [Abstract] [Full Text] [PDF]

				A. Papapetropoulos, R. D. Rudic, and W. C Sessa Molecular control of nitric oxide synthases in the cardiovascular system Cardiovasc Res, August 15, 1999; 43(3): 509 - 520. [Abstract] [Full Text] [PDF]

				D. W. Powell, R. C. Mifflin, J. D. Valentich, S. E. Crowe, J. I. Saada, and A. B. West Myofibroblasts. II. Intestinal subepithelial myofibroblasts Am J Physiol Cell Physiol, August 1, 1999; 277(2): C183 - C201. [Abstract] [Full Text] [PDF]

				D. W. Powell, R. C. Mifflin, J. D. Valentich, S. E. Crowe, J. I. Saada, and A. B. West Myofibroblasts. I. Paracrine cells important in health and disease Am J Physiol Cell Physiol, July 1, 1999; 277(1): C1 - C19. [Abstract] [Full Text] [PDF]

				B. Braam Renal endothelial and macula densa NOS: integrated response to changes in extracellular fluid volume Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1999; 276(6): R1551 - R1561. [Abstract] [Full Text] [PDF]

				T. Massfelder and J.-J. Helwig Editorial: Parathyroid Hormone-Related Protein in Cardiovascular Development and Blood Pressure Regulation Endocrinology, April 1, 1999; 140(4): 1507 - 1510. [Full Text]

				R. Wiest, V. Shah, W. C. Sessa, and R. J. Groszmann NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G1043 - G1051. [Abstract] [Full Text] [PDF]

				F. Rodriguez-Pascual, M. Hausding, I. Ihrig-Biedert, H. Furneaux, A. P. Levy, U. Forstermann, and H. Kleinert Complex Contribution of the 3'-Untranslated Region to the Expressional Regulation of the Human Inducible Nitric-oxide Synthase Gene. INVOLVEMENT OF THE RNA-BINDING PROTEIN HuR J. Biol. Chem., August 18, 2000; 275(34): 26040 - 26049. [Abstract] [Full Text] [PDF]

				J. G. Kiang, S. C. Kiang, Y.-T. Juang, and G. C. Tsokos Nomega -nitro-L-arginine inhibits inducible HSP-70 via Ca2+, PKC, and PKA in human intestinal epithelial T84 cells Am J Physiol Gastrointest Liver Physiol, March 1, 2002; 282(3): G415 - G423. [Abstract] [Full Text] [PDF]

				D. Saur, W. L. Neuhuber, B. Gengenbach, A. Huber, V. Schusdziarra, and H.-D. Allescher Site-specific gene expression of nNOS variants in distinct functional regions of rat gastrointestinal tract Am J Physiol Gastrointest Liver Physiol, February 1, 2002; 282(2): G349 - G358. [Abstract] [Full Text] [PDF]