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Ming-Hui Zou, MD, PhD
Professor, Paul H. and Doris Eaton Travis Chair in Endocrinology
Director, Vascular Biology Program

 

Dr. Zou's Research Group

Zou
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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

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Research Interests

Dr. Zou’s ongoing research programs look at the means to sense oxidative stress, reduce it, or ameliorate the body’s adverse response to it.  Dr. Zou has been 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 research 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 in research which have been recognized by many other investigators in the fields. Dr. Zou is an independent investigator of the National Institutes of Health, American Diabetes Association, and the Juvenile Diabetes Research Foundation International (JDRF) and a recipient of Scientist Development Award (SDG) and National Established Investigator (EIA) Award of the American Heart Association.  Dr. Zou has used these (and many other awards) to make scientific observations in the field with great potential for immediate clinical relevance. He has served on several national and international 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, membership in which reflects accomplishments by its members at an early stage in their careers and one of the United States’ oldest honor societies of physician-scientists.

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Education

1999 Dr. Rernat. University of Konstanz, Germany
1994 PhD - Paul-Sabatier University, France
1988 MSc - Hubei Medical University, China
1985 MD - Hubei Medical University, China

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Recent Publications

Wang S, Dale G, Song P, Viollet B, and Zou MH. (2010). AMPK alpha 1 deletion shortens erythrocyte lifespan in mice, role of oxidative stress. J. Biol. Chem., in press. PMID: 20392689.

Li YJ, Wang PH, Chen C, Zou MH, and Wang DW. (2010). Improvement of mechanical heart functions by trimetazidine in db/db mice. Acta Pharmacol Sin. in press. PMID: 20383170.
 
Liu C, Liang B, Wu J, and Zou MH. (2010). Activation of the AMP-activated protein kinase alpha 1 alleviates endothelial cell apoptosis by increasing the expression of anti-apoptotic proteins BCL-2 and survivin.J. Biol. Chem., in press. PMID 20233722.

Dong Y, Zhang M, Wang S, Liang B, Zhao Z, Liu C, Wu M, Choi H, Lyons T, and Zou MH.  (2010). Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes, Mar 18 2010. PMID 20299472.

Wang S, Zhang M, Xie Z, Viollet B, and Zou MH. (2010). AMPKalpha2 deletion accelerates atherosclerosis by increasing 26S proteasome-dependent degradation of I-kappa B and NAD(P)H oxidase expression. Circulation Research 106:1117-28. PMID: 20167927.

Dong Y, Zhang M, Liang B, Xie Z, Choi H, and Zou MH. (2010). Reduction of AMP-activated protein kinase alpha 2 increased endoplasmic reticulum stress and atherosclerosis in vivo. Circulation 121(6):792-803. PMID: 20124121.

Dong Y, Wu Y, Wu M, Wang S, Zhang Y, Xie Z, Xu J, Song P, Wilson K, Zhao Z, Lyons T, and Zou MH.  (2009). Activation of the Calcium-Dependent µ-Calpain by Oxidized and Glycated LDL Triggers the Degradation of Endothelial Nitric Oxide Synthase. J. Cell. Mol. Med. 13: 2899-2910. PMID: 18624772.

Xu J, and Zou MH. (2009). Molecular Insights and Therapeutic Targets for Diabetic Endothelial Dysfunction. Circulation. 120(13):1266-86.

Xu J, Wang S, Wu Y, Song P, and Zou MH. (2009). Tyrosine nitration of PA700 activates 26S proteasomes to induce endothelial functions in angiotensin II-induced hypertension. Hypertension. 54:625-632.

Wang S, Zhang M, Xu J, Song P, and Zou MH. (2009). In Vivo Activation of AMP-activated Protein Kinase Attenuates Diabetes-enhanced Degradation of GTP Cyclohydrolase I. Diabetes. 58(8):1893-901.

Song P, Zhang M, and Zou MH. (2009). Thromboxane receptor activates a ROCK/LKB1/PTEN to attenuate endothelium insulin signaling. J. Biol. Chem. 284(25):17120-8.

Xie Z, Dong Y, Zhang Y, Choi HC, and Zou MH. (2009). Identification of the Serine 307 of LKB1 as a Novel Phosphorylation Site Essential for its Nucleus Export and the Activation of AMP-activated Protein Kinase. Mol. Cell Biology. 29(13):3582-96.

Xie Z, Song P, Zhang M, and Zou MH. (2008). Up-regulation of Mitochondrial Uncoupling Protein-2 by the AMP-activated Protein Kinase in Endothelial Cells Attenuates Oxidative Stress in Diabetes. Diabetes. 57(12):3222-30.

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

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

Dong Y, Wu Y, Wu M, Wang S, Zhang Y, Xie Z, Xu J, Song P, Wilson K, Zhao Z, Lyons T, and Zou MH. (2008). 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, and Zou MH. (2008). Gene Silencing of GTP cyclohydrolase 1 by small RNA interference uncouples endothelial nitric oxide synthase in vivo. Hypertension. 52(3):484-90.

Choi HC, Song P, Xie Z, Wu Y, Xu J, Zhang M, Dong Y, Wang S, Lau K, and Zou MH. (2008). 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.

Song P, Wu Y, Xu J, Xie Z, Dong Y, Zhang M, and Zou MH. (2008). 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.

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

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

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

Xie Z, Dong Y, Zhang M, Cui MZ, Cohen RA, Riek U, Neumann D, Schlattner U, and Zou MH. (2008). 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.

Zou MH. (2007). DNA hypomethylation and endothelial degeneration in hyperhomocysteinemia. Blood 100:3495-3496.

Song P, Wu Y, Xu J, Xie Z, Dong Y, Zhang M, and Zou MH. (2007). 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.

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

An Z, Wang H, Song P, Zhang M, Geng X, and Zou MH. (2007). 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.

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

Zou MH. (2007). Peroxynitrite and protein tyrosine nitration of prostacyclin synthase. Prostaglandins and Related Lipid Mediators. 82:119-127.

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

Xu J, Xie Z, Reece R, Pimental D, and Zou MH. (2006). 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.

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

Davis B, Wiles IV WG, Xie Z, Viollet B, and Zou MH. (2006). 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.

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

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

Schulz E, Anter E, Zou MH, and Keaney, Jr JF. (2005). Estradiol-mediated eNOS association with heat shock protein 90 requires AMP-dependent protein kinase. Circulation. I 111:3473-80.

Zou MH, Kirkpatrick SS, Davis BJ, Brownlee M, and Wiles WG. (2004). 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.

Zou MH, Cohen RA, and Ullrich V. (2004). Sources and actions of oxidants in diabetic vessels. Endothelium. 11:89-97.

Zou MH, Hou XY, Shi CM, and Cohen RA. (2003). 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.

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

Gao W, Adachi T, Matsui R, Xu S, Jiang B, Zou MH, Kirber M, Lieberthal W, and Cohen RA. (2003). 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.
 
Bachschnidt M, Thurau S, Zou MH, and Ullrich V. (2003). Endothelial cell activation by endotoxin involves superoxide/NO mediated nitration of prostacyclin synthase and thromboxane receptor stimulation. FASEB J. 17: 914-6.

Ruderman NB, Caciedo J, Itani S, Yagihashi N, Saha AK, Ye J, Chen K, Zou MH, Carling D, and Cohen RA. (2003). Malonyl CoA and AMPK:  Possible Links Between Insulin Resistance in Muscle and Early Endothelial Cell Damage in Diabetes. Biochem. Soc. Trans., 31:202-6.

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

Zou MH, Hou XY, Shi S, Nagata D, Walsh KX, and Cohen RA. (2002). Modulation by peroxynitrite of Akt- and AMP activated kinase-dependent serine 1179 phosphorylation of endothelial nitric oxide synthase. J. Biol. Chem. 277:32552-32557.

Zou MH, Shi S, and Cohen RA. (2002). Oxidation by peroxynitrite of zinc-thiolate cluster of eNOS uncouples the enzyme in diabetes. J. Clin Invest. 109:817-826.

Zou MH, Shi C, and Cohen RA. (2002). 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.

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