Biochemistry & Cancer Biology

Amir Askari, Ph.D.

Professor

Telephone: (419) 383-4131, 383-3982
FAX: (419) 383-6228


e-mail: Amir.Askari@utoledo.edu


Training
  • B.S., Biology, 1953, University of Dubuque, Dubuque, Iowa
  • M.S., Chemistry, 1956, New York University
  • Ph.D., Biochemistry, 1960, Cornell University Medical College
Appointments
  • Instructor, Pharmacology, Cornell University Medical College, 1963-1964
  • Assistant Professor of Pharmacology, Cornell University Medical College, 1964-1967
  • Associate Professor of Pharmacology, Cornell University Medical College, 1967-1973
  • Acting Chairman, Pharmacology, Cornell University Medical College, 1971-1972
  • Professor of Pharmacology, Cornell University Medical College, 1973-1975
  • Professor of Physiology and Biophysics, Graduate School of Medical Sciences, Cornell University Medical College, 1973-1975
  • Professor and Chairman of Pharmacology and Therapeutics, Medical University of Ohio, 1975-1997
  • Professor of Pharmacology and Therapeutics, 1997-2005
  • Professor and Chairman, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, 2006-2009
  • Professor of Pharmacology and Therapeutics, 2010
  • Professor, Department of Biochemistry & Cancer Biology, University of Toledo College of Medicine, Health Science Campus, 2011-
Research Interests:

The laboratory has had a long-standing interest in the mechanism of ion transport across biological membranes, with a major emphasis on the properties and functions of (Na+,K+)-ATPase (the sodium pump) of the eucaryotic plasma membrane.  Current work of the laboratory is primarily on the digitalis-induced interactions of (Na+,K+)-ATPase with non-ATPase proteins, leading to the newly discovered functions of (Na+,K+)-ATPase as a signal transducer that regulates growth of the cardiac myocyte.  Recent findings include the discovery that digitalis drugs induce cardiac hypertrophy through the activation of P13K/Akt signaling pathways, and that this drug-induced hypertrophy is akin to physiological rather than pathological cardiac hypertrophy.  We are funded by NIH to test the hypothesis that low-dose digitalis treatment prevents hypertension-induced cardiac hypertrophy and failure.

Representative Publications

Morrill, G.A., Kostellow, A.B., and Askari, A.  (2008) Progesterone binding to the alpha1-subunit of the Na/K-ATPase on the cell surface: insights from computational modeling.  Steroids.  Jan; 73(1):27-40.

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(5):C1489-497.

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(1-2):231-237.

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(8):28-30.

Liu, L. and Askari, A. (2006) The beta-subunit of cardiac Na+/K+-ATPase dictates the concentration of the functional enzyme in caveolae.  Am J. Physiol Cell Physiol 291: C569-C578.

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, J., 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.

Liu, L., Mohammadi, K., Aynafshar B., Wang, H., Li D., Liu J., Ivanov, AV., Xie, Z., and Askari, A. (2003) Role of caveolae in the signal transducing function of cardiac Na+/K+-ATPase. Am. J. Physiol. 284:C1550-C1560.

Mohammadi, K., Liu, L., Tian, J., Kometiani, P., Xie, Z., and Askari, A. (2003) The positive inotropic effects of ouabain on the isolated heart is accompanied by the activation of signal pathways that link Na/K-ATPase to ERK1/2. J. Cardiovasc. Pharmacol. 41:609-614.

Ivanov, A.V., Modyanov, N.N., and Askari, A. (2002) Role of the self-association of beta-subunits in the oligomeric structure of Na+/K+-ATPase. Biochem. J. 364:293-299.

Xie, Z. and Askari, Z. (2002) Na+/K+-ATPase as a signal transducer. Eur. J. Biochem. 269:2434-2439.

Mohammadi, K., Kometiani, P., Xie, Z., and Askari, A. (2001) Role of protein kinase C in the signal pathways that link Na+/K+-ATPase to ERK1/2. J. Biol. Chem. 276:42050-42056.

Kometiani, P., Askari, A., Liu, J., Xie, Z., and Askari, F.K. (2000) Downregulation of cardiac myocyte Na+/K+-ATPase by adenovirus-mediated expression of an alpha-subunit fragment. Am. J. Physiol. 280:H415-H421

Askari, A. (2000) Significance of Protein-Protein Interactions to Na+/K+-ATPase Functions. in Na/K-ATPase and Related ATPase, K. Taniguchi and S. Kaya, Eds., pp. 17-26, Excerpta Medica Internat. Congress Series 1207, Elsevier, Amsterdam.

Liu, J., Tian, J., Haas, M., Shapiro, J.I., Askari, A., and Xie, Z. (2000) Ouabain interaction with cardiac Na+/K+-ATPase initiates signal cascades independent of changes in intracellular Na+ and Ca2+ concentrations. J. Biol. Chem. 275:27838-27844.

Haas, M., Askari, A., and Xie, Z. (2000) Involvement of Src and epidermal growth factor receptor in the signal transducing function of Na+/K+-ATPase. J. Biol. Chem. 275:27832-27837.

Xie, Z., Kometiani, P., Liu, J., Li, J., Shapiro, J.I., and Askari, A. (1999): Intracellular reactive oxygen species mediate the linkage of Na+/K+- ATPase to hypertrophy and its marker genes in cardiac myocytes. J. Biol. Chem. 274:19323-19328.

Kometiani, P., Li, J., Gnudi, L., Kahn, B.B., Askari, A., and Xie, Z. (1998): Multiple signal transduction pathways link Na+/K+-ATPase to growth- related genes in cardiac myocytes. J. Biol. Chem. 273:15249-15256.

Ivanov, A., Askari, A., and Modyanov, N.N. (1997): Structural analysis of the products of chymotryptic cleavage of the E1 form of Na,K-ATPase alpha- subunit: identification of the N-terminal fragments containing the transmembrane H1-H2 domain. FEBS Lett. 420:107-111.

Liu, L. and Askari, A. (1997): Evidence for the existence of two ATP- sensitive Rb+ occlusion pockets within the transmembrane domains of Na+/K+- ATPase. J. Biol. Chem. 272:14380-14386.

Sarvazyan, N.A., Ivanov, A., Modyanov, N.N., and Askari, A. (1997): Ligand-sensitive interactions among the transmembrane helices of Na+/K+- ATPase. J. Biol. Chem. 272:7855-7858.

Liu, G., Xie, Z., Modyanov, N.N., and Askari, A. (1996): Restoration of phosphorylation capacity to the dormant half of the alpha-subunits of Na+,K+- ATPase. FEBS Lett. 390:323-326.

Xie, Z., Wang, Y., Liu, G., Zolotarjova, N., Periyasamy, S.M., and Askari, A. (1996): Similarities and differences between the properties of native and recombinant Na+/K+-ATPases. Arch. Biochem. Biophys. 330:153-162.

Sarvazyan, N.A., Modyanov, N.N., and Askari, A. (1995): Intersubunit and intrasubunit contact regions of Na+/K+-ATPase revealed by controlled proteolysis and chemical cross-linking. J. Biol. Chem. 270:26528-26532.

Last Updated: 3/22/15