Mei-Zhen Cui, MS, Ph.D.
College of Veterinary Medicine
The University of Tennessee
A236, 2407 River Drive
Knoxville, TN 37996
- B.S., Jilin University, Changchun, China, 1982, Chemistry
- M.S., Jilin University, Changchun, China, 1985, Biochemistry
- Ph.D., Tokyo Institute of Technology, Japan, 1990, Molecular Biology
- Graduate Course CEM 609: Mechanisms of Disease
- Training graduate students and postdoctoral fellows
- Postdoctoral Fellow, The Scripps Research Institute, California, 1990-1994, Vascular Biology.
- Research Associate, Cleveland Clinic Foundation, Ohio, 1995-1999, Vascular Biology.
- Smooth muscle cell gene expression
- Signal transduction
- Mechanism of cardiovascular disease
The central objective of the research in our laboratory is to understand the molecular mechanism underlying vascular diseases specifically atherosclerosis and thrombosis. We have found that thrombin activates protein kinase D (PKD) invascular smooth muscle cells. Our results revealed a novel function of PKC δ in mediating thrombin-induced PKD activation and identified PKD as a new component in thrombin-induced intracellular signaling pathway in smooth muscle cells. Tissue factor, the initiator of the coagulation cascade, is expressed by cells in atherosclerotic lesions. Our data have shown that lysophosphatidic acid (LPA), a component of oxidized lipoproteins and an agent released by activated platelets, markedly induces tissue factor messenger RNA, tissue factor protein, and tissue factor activity in vascular smooth muscle cells. Activation of MEKs and ERKs mediates LPA-induced TF expression. Our results suggest that elevated LPA could be a thrombogenic risk factor. We are studying the regulation of tissue factor expression by components of oxidized low density lipoproteins and attempting to define the role of oxidized lipids in atherosclerosis and thrombosis.
- American Heart Association
- American Society for Biochemistry and Molecular Biology
- Xu, X., Shi Y., Wei, G., Mao, G., Zhao, G., Agrawal, S., Chisolm, G., and Cui, M.-Z., The novel presenilin-1-associated protein (PSAP) is a pro-apoptotic mitochondrial protein. J. Biol. Chem. 2002. 277(50): 48913-48922
- Cui, M.-Z., Zhao, G., Winokur, A., Laag, E., Bydash J. R., Penn, M. S., Chisolm G. M., and Xu, X., Lysophosphatidic Acid Induction of Tissue Factor Expression in Aortic Smooth Muscle Cells. Artherioscler, Thromb and Vasc Biol. 2003; 23:224-230
- Tan, M., Xu, X., Ohba, M., Ogawa W. and Cui, M.-Z., Thrombin rapidly induces protein kinase D phosphorylation and protein kinase C delta mediates the activation. J. Biol. Chem. 2003, 278(5): 2824-2828.
- Cui, M.-Z. and Xu, X., (invited commentary) Lysophosphatidic Acid, Tissue Factor and Atherosclerosis, 2003, at: http://www.athero.org
- Tan, M., Xu, X., Ohba, M. and Cui, M.-Z., Protein kinase C delta mediates Angiotensin II-induced protein kinase D phosphorylation in aortic smooth muscle cells. Artherioscler, Thromb and Vasc Biol. 2004, 24:2271-2276.
- Zhao G, Mao G, Tan J, Dong Y, Cui M.-Z., Kim SH, Xu X. Identification of a new presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein. J. Biol. Chem. 2004, 279(49): 50647-50650.
- Zhao, G., Cui M.-Z., Mao, G., Tan, J,, Dong Y, Sun, L. and Xu, X. (2005), γ-cleavage is dependent on ζ-cleavage during the proteolytic processing of amyloid precursor protein within its transmembrane domain. J. Biol. Chem., 2005. 280(45): 37689-37697.
- Dong, Y., Tan, J. Cui, M. Z., Zhao, G., Mao, G. Singh, N. and Xu, X., Calpain inhibitor MDL28170 modulates Aβ formation by inhibiting the formation of intermediate Aβ 46 and protecting Aβ from degradation. The FASEB Journal, 2006, 20: 331-333.
- Xie, Z., Dong, Y., Zhang, M., Cui, M. Z., Cohen, R.. Riek, U., Neumann, D., Schlattner, U., Zou, M.-H. Activation of Protein kinase C-ζ by Peroxynitrite Regulates LKB1-dependent AMP-activated Protein Kinase in Cultured Endothelial Cells. J. Biol. Chem. 2006; 281(10): 6366-6375.
- Cui, M. Z., Laag, E., Sun, L., Tan, M., Zhao G., and Xu, X., Lysophosphatidic Acid Induces Early Growth Response Gene 1 Expression in Vascular Smooth Muscle Cells, CRE and SRE Mediate the transcription, Artherioscler, Thromb and Vasc Biol. 2006; 26: 1029-1035
- Zhao, G., Tan, J., Mao, G., Cui, M.-Z., and Xu, X., The sequential relationship of the multi intramembrane cleavages of APP suggests a single enzyme model, J. Neurochem, 2007, 100: 1234-1246.
- Hao, F., Tan, M., S., Xu, X., Han, J., Miller, D., Tigyi, G., and Cui, M.-Z. Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA1, p42 and p38α, Biochim Biophys Acta- Mol and Cell Bio Lipid, 2007, 1771: 883-892
- Mao, G., Dong, Y., Tan, J., Cui, M. Z. and Xu, X. Both the N-terminal fragment and the protein-protein interaction domain (PDZ domain) are required for the pro-apoptotic activity of presenilin-associated protein PSAP, Biochim Biophys Acta. 2008, 1780(4):696-708
- Hao, F., Tan, M., Xu, X., and Cui, M.-Z. Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-Mediated Protein Kinase Cδ-Dependent ERK Activation Pathway, J. Biol. Chem. 2008, 283(40): 26928-26936
- Tan, J., Mao, G., Cui M.-Z., Kang, S.C., Lamb, B., Wong, B.S., Sy, M.S., Xu, X. Effects of gamma-secretase cleavage-region mutations on APP processing and Abeta formation: interpretation with sequential cleavage and alpha-helical model. J. Neurochem. 2008, 107, 722-733.
- Tan, M., Hao, F., Xu, X., Chisolm, G. and Cui M.-Z., Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocytic THP-1 cell migration, Arterioscler Thromb Vasc Biol. 2009; 29:1376-1382.
- Mao, G., Tan, J., Cui M.-Z., Chui, D. and Xu, X. The GxxxG Motif in the Transmembrane Domain of AβPP Plays an Essential Role in the Interaction of CTFβ with the γ-secretase Complex and the Formation of Aβ. Journal of Alzheimer’s Disease, 2009; 18(1):167-176
- Tan, J., Mao, G., Cui M.-Z., Lamb, B., Sy, M.-S. and Xu, X. Residues at P2-P1 positions of epsilon- and zeta-cleavage sites are important in formation of beta amyloid peptide. Neurobiology of Disease. 2009; 36(3):453-460
- Hao, F. Tan, M. Wu, D. Xu, X. and Cui M.-Z., Lysophosphatidic acid induction of interleukin 6 secretion from aortic smooth muscle cells via LPA1 regulated, PKC dependent and p38alpha mediated pathway, American Journal of Physiology-Heart and Circulatory Physiology, December 2009; in press.