Ming-Hui Zou, MD, PhD Professor, Paul H. and Doris Eaton Travis Chair in Endocrinology Director, Vascular Biology Program   Dr. Zou's Research Group
Mailing Address: 941 Stanton L. Young Blvd., BSEB 306A Oklahoma City, OK 73104	Telephone: (405) 271-3974 Fax: (405) 271-3973
Email: ming-hui-zou@ouhsc.edu

Research Interests

Means to sense oxidative stress, reduce it, or ameliorate the body’s adverse response to it are central to Dr. Zou’s ongoing research programs. Dr. Zou was instrumental in examining the role of nitric oxide and oxidative stress in the regulation of blood flow and vascular function. He performed elegant, state of the art, studies to show that the selective modification of two key proteins, prostacyclin synthase and endothelial nitric oxide synthase, is critical in the dysregulation of vessel function from nitric oxide and superoxide. Dr. Zou’s group was also the first to demonstrate that the AMP-activated kinase (AMPK), a key enzyme in the regulation of energy metabolism, obesity, diabetes, and cardiovascular diseases, functions as a sensor and regulator of oxidative stress. Dr. Zou’s contributions in this area are important and his work represents outstanding breakthroughs research which has been recognized by many other investigators in the fields. An independent investigator of the National Institutes of Health and the Juvenile Diabetes Research Foundation International (JDRF) and a National Scientist Development awardee of the American Heart Association, Dr. Zou has used these (and many other awards) to make scientific observations in fields with great potential for immediate clinical relevance. He has served on several national study panels such as the National Institutes of Health and American Heart Association. In 2008 he was elected to the American Society for Clinical Investigation, one of the US’ oldest honor societies of physician-scientists, membership in which reflects accomplishments by its members at an early stage in their careers.

Education

Xie, Z., Song, P., Zhang, M., Zou, M.H. Up-regulation of Mitochondrial Uncoupling Protein-2 by the AMP-activated Protein Kinase in Endothelial Cells Attenuates Oxidative Stress in Diabetes. Diabetes. In press.

Zhang, J., Xie, Z., Wang, S., Zou, M.H. Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Endothelial Cells. J. Biol. Chem. 283(41):27452-61, 2008.

Zhang S, Wang J, Dashti A, Wilson K, Szweda L, Zou, M. H, Lyons T, Ma JX. Pigment epithelium-derived factor (PEDF) mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized-LDL. J. Mol. Endocrinol. 41(3):135-43, 2008.

Dong, Y., Wu, Y., Wu, M., Wang, S., Zhang, Y., Xie, Z., Xu, J., Song, P., Wilson, K., Zhao, Z., Lyons, T., Zou, M.H. Activation of the Calcium-Dependent µ-Calpain by Oxidized and Glycated LDL Triggers the Degradation of Endothelial Nitric Oxide Synthase. J. Cell. Mol. Med. In press.

Wang, S., Xu, J., Song, P., Wu, Y., Zou, M.H. Gene Silencing of GTP cyclohydrolase 1 by small RNA interference uncouples endothelial nitric oxide synthase in vivo. Hypertension. 52(3):484-90, 2008

Choi HC, Song P, Xie Z, Wu Y, Xu J, Zhang M, Dong Y, Wang S, Lau K, Zou MH. Protein Kinase C-z Dependent Serine 428 Phosphorylation and Nuclear Export of LKB1 Is Required for Statins-induced Activation of the AMP-activated Kinase. J. Biol. Chem. 283(29):20186-97, 2008

Song P, Wu Y, Xu J, Xie Z, Dong Y, Zhang M, Zou MH. Protein kinase C ζ-dependent LKB1 phosphorylation at Ser428 induced LKB1 nuclear export and apoptosis in endothelial cells. J. Biol. Chem. 283(18):12446-55, 2008

Wenzel, P., Daiber, A., Oelze, M., Brandt, M., Closs, A., Xu, J., Thum, T., Bauersachs, J., Ertl, G., Zou, M.H., Förstermann, U., Münzel, T. Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus.Atherosclerosis 198(1):65-76, 2008

Wu, Y. and Zou, M.H. Activation of the AMP-activated kinase as a strategy of protecting endothelial function. Clinical and Experimental Pharmacology and Physiology. 35, 535–545, 2008

Zhang M., Dong, Y., Xu, J., Xie, Z., Wu, Y., Song, P., Guzman, M., and Zou, M-H. Thromboxane receptor via hydrogen peroxide activates the AMP-activated kinase in vascular smooth muscle cells. Circulation Research 102:328-337, 2008

Xie Z, Dong Y, Zhang M, Cui MZ, Cohen RA, Riek U, Neumann D, Schlattner U, Zou MH. Phosphorylation of LKB1 at serine 428 by protein kinase C-z is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Circulation 117:952-962, 2008

Zou, M.H. DNA hypomethylation and endothelial degeneration in hyperhomocysteinemia. Blood 100:3495-3496, 2007

Song, P., Wu, Y., Xu, J., Xie, Z., Dong, Y., Zhang, M., and Zou, M.H. Reactive Nitrogen Species Caused by Hyperglycemia Suppresses Protein Kinase B/Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN in an LKB1-dependent Manner.  Circulation 116;1585-1595; 2007;

Xu, J., Wu, Y., Song, P., Zhang, M., Zou, M.H. Proteasome-dependent degradation of GTP-cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes. Circulation 116(8):944-53, 2007.

An, Z., Wang, H., Song, P., Zhang, M., Geng, X., Zou, M.H. Nicotine-activated AMP-activated protein kinase inhibits fatty acid synthase in 3T3-L1 adipocytes: a role of oxidant stress. J. Biol. Chem. 282(37): 26793 – 26801, 2007

Wu, Y., Song, P., Xu, J., Zhang, M., Zou, M.H. Activation of protein phosphatase PP2A by palmitatic acid inhibits the AMP-activated protein kinase (AMPK). J. Biol. Chem. 282(13):9777-88, 2007

Zou, M.H. Peroxynitrite and protein tyrosine nitration of prostacyclin synthase. Prostaglandins and Related Lipid Mediators. 82:119-127, 2007

Nie, H. Wu, J., Zhang, M., Xu, J., and Zou, M.H. Endothelial nitric oxide synthase-dependent tyrosine nitration of prostacyclin synthase in diabetes mellitus in vivo. Diabetes 55(11):3133-41, 2006.

Xu, J., Xie, Z., Reece, R., Pimental, D., Zou, M.H. Hypochlorous acid uncouples endothelial nitric oxide synthase: Role of vascular NAD(P)H oxidase-derived superoxide and peroxynitrite. Arteriosclerosis, Thrombosis, and Vascular Biology. 26:2688-95, 2006.

Du, X., Edelstein, D., Zou, M.H., Brownlee, M. Insulin resistance causes proatherosclerotic changes in arteries by increasing arterial endothelial cell fatty acid oxidation. J. Clin. Invest.  116(4):1071-80, 2006.

Davis, B., Wiles IV, W. G., Xie, Z., Viollet, B., Zou, M.H. Activation of the AMP-activated kinase by anti-diabetic drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes, 55:496-505, 2006.

Xie, Z., Davis, B., Zhang, M., Cui, M.Z., Riek, U., Neumann, D., Shi, C., Hou, X., Cohen, R., Zou, M.H. Activation of protein kinase-C by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in endothelial cells. J. Biol. Chem. 281:6366-75, 2006.

Davis, B. and Zou, M.H. CD40Ligand (CD40L)-dependent tyrosine nitration of prostacyclin synthase in vivo. Circulation. 112(14):2184-92, 2005.

Schulz, E., Anter, E., Zou, M.H., and Keaney, J.F. Jr. Estradiol-mediated eNOS association with heat shock protein 90 requires AMP-dependent protein kinase. Circulation. I 111:3473-80, 2005.

Zou, M.H., Kirkpatrick S. S., Davis, B. J., Brownlee, M., Wiles, W. G. Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin is mediated through mitochondrial reactive oxygen species and PI-3 kinase. J. Biol. Chem. 279:43940-51, 2004.

Zou, M.H. H., Cohen, R. A., and Volker Ullrich. Sources and actions of oxidants in diabetic vessels. Endothelium. 11:89-97, 2004.

Zou, M.H., Hou, X. Y., Shi, C.M., Cohen, R. A. Activation of 5’AMP-activated kinase is mediated through c-Src and PI-3 kinase activity during hypoxia-reoxygenation of bovine aortic endothelial cells: Role of Peroxynitrite. J. Biol. Chem. 278:34003-34010, 2003.

Hink, U., Oelze, M., Kolb, P., Bachschmid M., Zou, M.H., Daiber, A., Mollnau, H., August, M., Baldus, S., Tsilimings, N., Walter, U., Ullrich, V., Munzel, T. Nitroglycerin induced peroxynitrite formation inhibits vascular prostacyclin synthesis via tyrosine nitration of the prostacyclin synthase. J. Am. Coll. Cardiol. 42(10), 2003.

Gao, W., Adachi, T, Matsui, R., Xu, S., Jiang, B., Zou, M.H., Kirber, M., Lieberthal, W., and Cohen, R. A. Quantitative Assessment of Tyrosine Nitration of Manganese Superoxide Dismutase in Angiotensin II-infused Rat Kidney. Am. J.  Physiol. Heart. Circ. Physiol. 285(4):H1396-403, 2003.
 
Bachschnidt, M., Thurau, S., Zou, M.H., Ullrich, V. Endothelial cell activation by endotoxin involves superoxide/NO mediated nitration of prostacyclin synthase and thromboxane receptor stimulation. FASEB J. 17: 914-6, 2003.

Ruderman, N.B., Caciedo, J., Itani, S., Yagihashi, N., Saha, A.K., Ye, J., Chen, K., Zou, M.H., Carling, D., Cohen, R.A. Malonyl CoA and AMPK:  Possible Links Between Insulin Resistance in Muscle and Early Endothelial Cell Damage in Diabetes. Biochem. Soc. Trans., 31:202-6, 2003.

Ullrich, V., Daiber, A., Bachschmid, M., Zou, M.H. Nitration of prostacyclin synthase: mechanism and physiological implications. International Congress Series. 1233:405-414, 2002.

Zou, M.H., Hou, X.Y., Shi, S., Nagata, D., Walsh, K.X., Cohen, R. A. Modulation by peroxynitrite of Akt- and AMP activated kinase-dependent serine 1179 phosphorylation of endothelial nitric oxide synthase. J. Biol. Chem. 277:32552-32557, 2002.

Zou, M.H., Shi, S., Cohen, R.A. Oxidation by peroxynitrite of zinc-thiolate cluster of eNOS uncouples the enzyme in diabetes. J. Clin Invest. 109:817-826, 2002.

Zou, M.H., Shi, C., Cohen, R. A. High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells. Diabetes. 51:198-203, 2002.