Within the past ten years, nitric oxide (NO) has been increasingly recognized as a versatile and important biological signaling molecule. In the cardiovascular system, NO has a key role in regulation of vascular tone, platelet aggregation, leukocyte adhesion, vascular smooth muscle cell proliferation, angiogenesis, and vascular lesion formation. NO is synthesized in the cardiovascular system by oxidation of L-arginine in a reaction catalyzed by the endothelial nitric oxide synthase (eNOS). In our laboratory, we have used a variety of biochemical and molecular biology techniques to study structure-function relationships in the eNOS enzyme. We are interested, second of all, in eNOS protein-protein interactions, especially with regard to how these interactions may regulate enzyme catalytic activity. Third we have recently begun to study the role of phosphorylation of eNOS in post-receptor signaling by the important eNOS-activating agonist, bradykinin.

Grant Support as Principal Investigator

National Institutes of Health, "Bradykinin Signaling in Regulation of eNOS"

American Heart Association, "Novel Protein Domains that Inhibit Endothelial Nitric Oxide Synthase"

Honors and Awards

• Drew Scholarship, University of Iowa, 1972-1974.
• Institutional National Research Service Award, Research Training Program in Endocrinology, Metabolism, and Diabetes, Emory University School of Medicine, 1991.
• Individual National Research Service Award for "Protein kinase C and regulation of cardiac contractility", 1992.
• Individual National Research Service Award for "Transcriptional regulation of nitric oxide synthase", 1993.
• Distinguished Faculty Award for Basic Science Research, Medical College of Georgia School of Medicine, 2000.
• Established Investigator of the American Heart Association, 2001-2004.
• International Scientific Advisory Board of the 2nd International Conference on the Biology, Chemistry, and Therapeutic Applications of NO, 2002.
• Fellow of the Council on Basic Cardiovascular Sciences of the American Heart Association (F.A.H.A.), 2002-present.

Lab

Chunying Li, Ph.D.: Postdoctoral Fellow

Sarika G. Sood, M.D.: Research Associate

Ling Ruan, M.S.: Research Associate

Virginia J. Venema, M.S.: Research Assistant

Selected Publications

Selected from over 70 publications

Venema, R.C., Sayegh, H.S., Arnal, J.F., and Harrison, D.G. (1995) Role of the enzyme calmodulin-binding domain in membrane association and phospholipid inhibition of endothelial nitric oxide synthase. J. Biol. Chem. 270, 14705-14711.

Venema, R.C., Sayegh, H.S., Kent, J.D., and Harrison, D.G. (1996) Identification, characterization, and comparison of the calmodulin-binding domains of the endothelial and inducible nitric oxide synthases. J. Biol. Chem. 271, 6435-6440.

Venema, R.C., Ju, H., Zou, R., Ryan, J.W., and Venema, V.J. (1997) Subunit interactions of endothelial nitric oxide synthase. Comparisons to the neuronal and inducible nitric oxide synthase isoforms. J. Biol. Chem. 272, 1276-1282.

Ju, H., Zou, R., Venema, V.J., and Venema, R.C. (1997) Direct interaction of endothelial nitric oxide synthase and caveolin-1 inhibits synthase activity. J. Biol. Chem. 272, 18522-18525.

Ju, H., Venema, V.J., Marrero, M.B., and Venema, R.C. (1998) Inhibitory interactions of the bradykinin B2 receptor with endothelial nitric oxide synthase. J. Biol. Chem. 273, 24025-24029.

Marrero, M.B., Venema, V.J., Ju, H., He, H., Liang, H., Caldwell, R.B., and Venema, R.C. (1999) Endothelial nitric oxide synthase interactions with G-protein-coupled receptors. Biochem. J. 343, 335-340.

Harris, M.B., Ju, H., Venema, V.J., Liang, H., Zou, R., Michell, B.J., Chen, Z., Kemp, B.E., and Venema, R.C. (2001) Reciprocal phosphorylation and regulation of the endothelial nitric oxide synthase in response to bradykinin stimulation. J. Biol. Chem. 276, 16587-16591.

Harris, M.B., Michell, B.J., Chen, Z., Ju, H., Venema, V.J., Blackstone, M.A., Huang, W., Kemp, B.E., and Venema, R.C. (2002) Identification of regulatory sites of phosphorylation of the bovine endothelial nitric oxide synthase at serine 617 and serine 635. J. Biol. Chem. 277, 42344-42351.

Harris, M.B., Blackstone, M.A., Ju, H., Venema, V.J., and Venema, R.C. (2003) Heat-induced increases in endothelial nitric oxide synthase expression and activity and endothelial NO release. Am. J. Physiol. 285, H333-H340.

Venema, R.C., Venema, V.J., Ju, H., Harris, M.B., Snead, C., Jilling, T., Dimitropoulou, C., Maragoudakis, M.E., and Catravas, J.D. (2003) Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. Am. J. Physiol. 285, H669-H678.

Harris, M.B., Blackstone, M.A., Sood, S.G., Li, C., Goolsby, J.M., Venema, V.J., Kemp, B.E., and Venema, R.C. (2004) Acute activation and phosphorylation of eNOS by HMG-CoA reductase inhibitors. Am. J. Physiol. 287, H560-H566.

Li, C., Huang, W., Harris, M.B., Goolsby, J.M., and Venema, R.C. (2005) Interaction of the endothelial nitric oxide synthase with the CAT-1 arginine transporter enhances NO release by a mechanism not involving arginine transport. Biochem. J. 386, 567-574.

Fulton, D., Church, J., Ruan, L., Li, C., Sood, S.G., Kemp, B.E., Jennings, I.G., and Venema, R.C. (2005) Src kinase activates endothelial nitric oxide synthase by phosphorylating Tyr-83. J. Biol. Chem. 280, 35943-35952.

Harris, M.B., Bartoli, M., Sood, S.G., Matts, R.L., and Venema, R.C. (2006) Direct interaction of cell division homology 37 inhibits endothelial nitric oxide synthase activity. Circ. Res. 98, 335-341.

Jackson, S.J.T. and Venema, R.C. (2006) Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. J. Nutr. 136, 1178-1184.

Education and Training

Research Experience & Academic Appointments

Institutional Faculty List

Society Memberships

• American Association for the Advancement of Science
• American Heart Association Council on Basic Cardiovascular Sciences
• American Society for Biochemistry and Molecular Biology
• Society for Pediatric Research