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| Lijun Liu, M.D., M.S.
Signal transduction of Na/K-ATPase in the cardiovascular system and cancer cells
Current research in our laboratory is focused on the cardiac signaling of Na/K-ATPase in cardiac hypertrophy and heart failure. As the receptor of digitalis drugs, Na/K-ATPase not only pumps ions, but also functions as a signaling transducer. The delineation of the Na/K-ATPase-mediated signal transduction pathways are likely to present new avenues for therapeutic intervention and understanding of human cardiac disease mechanisms. We seek to achieve this goal through cutting edge basic research. We define ouabain-induced cardiac singnaling and cardiac effects in transgenic mouse model, surgical animal models and primary cultured cardiomyocyts. Our goal is to provide the scientific evidence for clinical use of digitalis.
Member of the mentoring faculty for the Biomedical Sciences Graduate Program (Cardiovascular and Metabolic Diseases)
1987-1992 M.D., Clinical Medicine, Capital Medical University, Beijing, China
1992-1995 M.S., Pharmacology, Capital Medical University, Beijing, China
|2011-present||Assistant Professor, Department of Biochemistry & Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, Ohio|
|2009-2011||Assistant Professor, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, Toledo, Ohio|
|2004-2009||Research Assistant Professor, Department of Physiology and Pharmacology, University of Toledo College of Medicine, HEalth Science Campus, Toledo, Ohio|
|1999-2004||Postdoctoral Fellow, Department of Pharmacology and Therapeutics, Medical University of Ohio, Toledo, Ohio|
|1995-1999||Assistant Professor, Chinese Academy of Preventative Medicine (Chinese Center for Disease Control and Prevention), Beijing, China|
Liu, L., Ivanov, A.V., Gable, M.E., Jolivel, F. Morrill, G.A., and Askari, A. (2011) Comparative properties of caveolar and noncaveolar preparations of kidney Na+/K+-ATPase. Biochemistry 50:8664-8673.
Liu, J., Yan, J., Liu, L., Xie, Z., Malhotra, D., Joe, B., and Shapiro, J.I. (2011) Impairment of Na/K-ATPase signaling in renal proximal tubule contributes to Dahl salt-sensitive hypertension. J Biol Chem 286:22806-22813.
Gopalakrishnan, K., Morgan, E.E., Yerga-Woolwine, S., Farms, P., Kumarasamy, S., Kalinoski, A., Liu, X., Wu, J., Liu, L., and Joe, B. (2011) Augmented rififylin is a risk factor linked to aberrant cardiomyocyte function, short-QT interval and hypertension. Hypertension 57:764-771.
Ye, Q., Li, Z., Tian, J., Xie, J.X., Liu, L., and Xie, Z. (2011) Identification of a potential receptor that couples ion transport to protein kinase activity. J Biol Chem 286:6225-6232.
Liu, L., Gable, M., Xie, Z., Lingrel, J.B. and Askari, A. (2010) Endogenous digitalis-like compounds may regulate cardiac hypertrophy/failure. Circulation 122:A9028.
Li Z, Cai T, Tian J, Xie JX, Zhao X, Liu L, Shapiro JI, and Xie Z. (2009) NaKtide, a Na/K-ATPase-derived peptide Src inhibitor, antagonizes ouabain-activated signal transduction in cultured cells. J Biol Chem 284:21066-21076.
Tian J, Li X, Liang M, Liu L, Xie JX, Ye Q, Kometiani P, Tillekeratne M, Jin R, and
Xie Z. (2009) Changes in sodium pump expression dictate the effects of ouabain on cell growth. J Biol Chem 284:14921-14929.
Cai, T., Wang, H., Chen, Y., Liu, L., Gunning, W.T., Quintas, L.E.M., and Xie, Z.-J. Regulation of caveolin-1 membrane trafficking by the Na/K-ATPase. J Cell Biol 182:1153-1169.
Li, D., Yang, C., Chen, Y., Tian, J., Liu, L., Dai, Q., Wan, X., and Xie, Z. (2008) Identification of a PKCepsilon-dependent regulation of myocardial contraction by epicatechin-3-gallate. Am J Physiol Heart Circ 294:H345-353.
Liu, L., Zhao, X., Pierre, S.V., and Askari, A. (2007) Association of PI3K-Akt signaling pathway with digitalis-induced hypertrophy of cardiac myocytes. Am J Physiol Cell Physiol 293:C1489-1497.
Liu, L., Gable, M.E., Garlid, K.D., and Askari, A. (2007) Interactions of K+ATP channel blockers with Na+/K+-ATPase. Mol Cell Biochem 306:231-237.
Liang, M., Tian, J., Liu, L., Pierre, S., Liu, J., Shapiro, J., and Xie, Z.J. (2007) Identification of a pool of non-pumping Na/K-ATPase. J Biol Chem 282:10585-10593.
Liu, L. and Askari, A. (2006) On the importance and mechanism of amplification of digitalis signal through Na+/K+-ATPase. Cell Mol Biol (Noisy-le-grand) 52:28-30.
Liu, L., Li, J., Liu, J., Yuan, Z., Pierre, S.V., Qu, W., Zhao, X., and Xie, Z. (2006) Involvement of Na+/K+-ATPase in hydrogen peroxide-induced hypertrophy in cardiac myocytes. Free Radic Biol Med 41:1548-1556.
Liu, L. and Askari, A. (2006) Beta-subunit of cardiac Na+-K+-ATPase dictates the concentration of the functional enzyme in caveolae. Am J Physiol Cell Physiol 291: C569-C578.
Tian, J., Cai, T., Yuan, Z., Wang, H., Liu, L., Haas, M., Maksimova, E., Huang, X., and Xie, Z. (2006) Binding of Src to Na+/K+-ATPase forms a functional signaling complex. Mol Biol Cell 17:317-326.
Liu, J., Liang, M., Liu, L., Malhotra, D., Xie, Z., and Shapiro, J. (2005) Ouabain-induced endocytosis of the plasmalemmal Na/K-ATPase in LLC-PK1 cells requires caveolin-1. Kidney Int 67:1844-1854.
Kometiani, P.K., Liu, L., and Askari, A. (2005) Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells. Mol Pharmacol 67:929-936.
Liu, L., Abramowitz, A., Askari, A., and Allen, J. (2004) Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle
cells of the synthetic phenotype. Am J Physiol Heart Circ Physiol 287:H2173-H2182.
Abramowitz, J., Dai, C., Hirschi, K.K., Dmitrieva, R.I., Doris, P.A., Liu, L., and Allen, J.C. (2003) Ouabain- and marinobufagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle cell line, A7r5. Circulation 108:3048-3053.
Liu, L., Mohadmmadi, K., Aynafshar, B., Wang, H., Li, D., Liu, J., Ivanov, A., Xie,
Z., and Askari, A. (2003) Role of caveolae in signal-transducing function of cardiac Na+/K+-ATPase. Am J Physiol Cell Physiol 284:C1550-C1560.
Mohammadi, K., Liu, L., Tian, J., Kometiani, P., Xie, Z., and Askari, A. (2003) Positive inotropic effect of ouabain on isolated heart is accompanied by activation of signal pathways that link Na+/K+-ATPase to ERK1/2. J Cardiovasc Pharmacol 41:609-614.
Liu, L., Mohammadi, K., Aynafshar, B., Wang, H., Li, D., Liu, J., Ivanov, A., Xie, Z., and Askari, A. (2003) Role of caveolae in signal-transducing function of cardiac Na+/K+-ATPase. Am J Physiol Cell Physiol 284:C1150-1160.
Li, N., Sun, Z., Liu, L., Han, C., and Chen, J. (2002) Chemopreventive effects of tea on human oral precancerous mucosa lesions. J. Hygiene Res. 31:441-443.
Liu, L. (2000) Trend in chemopreventive agents in colorectal carcinogenesis. (Review) Foreign Med. Sci. (Hygiene section) 27(1):6-10.
Liu, L., Han, C., and Chen, J. (1998) Short-term screening of anticarcinogenic ingredients of tea by cell biology assay. J. Hygiene Res. 27:53-56.
Liu, L (1996) Functional foods improve human health. J. of Chinese Functional Food 6:12.