Lijun Liu, M.D., M.S.
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 (Molecular Medicine)
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|
Akkuratov, E., Lopacheva, O., Kruusmägi, M., Lopachev, A., Shah, Z., Boldyrev, A., and Liu, L. (2015) Functional interaction between Na/K-ATPase and NMDA receptor in cerebellar neurons. Molecular Neurobiology 52:1726-1734.
Duan, Q., Madan, N.D., Wu, J., Kalisz, J., Doshi, K.Y., Haldar, S.M., Liu, L., and
Pierre, S.V. (2014) Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection induced
by ouabain preconditioning. J Mol Cell Cardiol 80:114-125.
Akkuratov, E., Wu, J., Sowa ,D., Shah, Zahoor A., and Liu, L. (2015) Ouabain-induced signaling and cell survival in SK-N-SH neuroblastoma cells differentiated by retinoic acid. CS & Neurological Disorders-Drug Targets 14:1343-1349.
Mehta, G., Kumarasamy, S., Wu, J,. Walsh, A., Liu, L., Williams, K., Joe, B., and de la Serna, I.L. (2015) MITF interacts with the SWI/SNF subunit, BRG1, to promote GATA4 expression in cardiac hypertrophy. J Mol Cell Cardiol 88:101-110.
Wu, J., Li, D., Du, L., Baldawi, M., Gable, M.E., Askari, A., and Liu, L. (2015) Ouabain prevents pathological cardiac hypertrophy and heart failure through activation of phosphoinositide 3-kinase alpha in mouse. BMC Cell & Biosci 5:64.
Abou Alaiwi, W.A, Muntean, B.S., Ratnam, S., Joe, B. Liu, L., Booth, R.L., Rodriguez I., Herbert, B.S., Bacallao, R.L., Fruttiger, M., Mak ,T.W., Zhou, J., and Nauli, S.M. (2014) Survivin-induced abnormal ploidy contributes to cystic kidney and aneurysm formation. Circ 129:660-672.
Gable, M.E., Abdallah, S.L., Najjar, S.M., Liu, L, and Askari, A. (2014) Digitalis-Induced cell signaling by the sodium pump: On the relation of SRC to NA+/K+-ATPase. Biochem Biophys Res Comm 446:1151-1154.
Li, D., Wu, J., Bai, Y., Zhao, X. and Liu, L. (2014) Isolation and culture of adult mouse cardiomycocytes for cell signaling and in vitro cardiac hypertrophy. J Vis Exp. May 21;(87).
Bai, Y., Morgan, E.E., Giovannucci, D.R., Pierre, S.V. Philipson, K.D., Askari, A., and Liu, L. (2013) Different roles of the cardiac Na+/Ca2+ exchanger in ouabain-induced inotrophy, cell signaling and hypertrophy. Am J Physiol Heart Circ Physiol 304:H427-H435.
Yan, Y., Shapiro, A.P., Haller, S., Katragadda, V., Liu, L., Tian, J. Basrur, V., Mahotra, D., Xie, J. Abraham, N.G., Shapiro, J.L. and Liu, J. (2013) The involvement of reactive oxygen species in a feed-forward mechanism of Na/K-ATPase mediate signaling transduction. J Biol Chem 288:34249-34258.
Wu, J., Akkuratov, E.E., Bai,Y., Gasdkill, C.M., Askari, A., and Liu, L. (2013) Cell signaling associated with Na+/K+-ATPase: Activation of PI3K/Akt by ouabain is independent of Src. Biochem 52;9059-9067.
Liu, C., Bai, Y., Chen, Y., Wang, Y., Sottejeau, Y., Liu, L., Li, X., Lingrel, J.B. ,Malhotra, D., Cooper, C.J., Shapiro, J.I., Xie, Z.J. and Tian, J. (2012) Reduction of Na/K-ATPase potentiates marinobufagenin-induced cardiac dysfunction and myocyte apoptosis. J Biol Chem 287:16390-16398.
Nesher, M., Bai, Y., Li, D., Rosen, H., Lichtstein, D. and Liu, L. (2012) Interaction of atrial natriuretic peptide and ouabain in the myocardium. Can J Physiol Pharmacol 90:1386-1393.
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.
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.
Quintas, L.E., Pierre, S.V., Liu, L., Bai, Y., Liu, X., and Xie, Z.J. (2010) Alteration of Na+/K+-ATPase function in caveolin-1 knockout cardiac fibroblasts. J Mol Cell Cardiol 49:525-531.
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.
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.