Jacob I. Sznajder

Jacob I. Sznajder, MD
Ernest S. Bazley Professor of Medicine
Chief, Pulmonary and Critical Care Medicine

Mediators and mechanisms of acute lung injury - regulation of Na,K-ATPase in the alveolar epithelium


In patients with acute hypoxemic respiratory failure (AHRF) lung airspaces flood with edema from damaged pulmonary vessels and alveolar membranes, thus interfering with oxygen transfer from the airspaces into the blood which results in hypoxemia, hypercapnia and death if corrective measures are not taken. Although most patients with AHRF die from complications of multiple-organ failure, several studies have suggested that strategies to reduce pulmonary edema are associated with shorter stays in the Intensive Care Unit and better outcomes. Several studies have demonstrated the importance of active Na+ transport in the alveolar fluid reabsorption and the survival of mechanically critically ill patients with AHRF that are placed on a mechanical respirator. Active Na+ transport in normal and injured lungs are mediated by alveolar epithelial apical Na+ channels and basolateral Na,K-ATPase. 

Na,K-ATPase maintains cellular ionic and electrochemical gradients through the hydrolysis of ATP coupled to the transport of Na+ and K+ across the plasma membrane. A functional Na,K-ATPase is a heterodimer composed of an a and b subunit. At least three isoforms of the a subunit have been described, (alpha-1, alpha-2 and alpha-3), each having different sodium affinity, ouabain sensitivity, and tissue distribution. The glycosylated b subunit is thought to be responsible for integrating the isoform into the plasma membrane; to date three b isoforms have been described. 

We study the regulation and role of the Na,K-ATPase in the lung epithelium and how this contributes to the lung ability to clear edema from the lungs. For these studies we utilize multiple approaches including cell and molecular biology in cells and monolayers as well as physiological models which allow for a "well rounded" scientific training.

Selected Publications:

Vadasz I., L. Dada, A. Briva, H. Trejo, L. Welch, J. Chen, P.T. Toth, E. Lecuona, L.A. Witters, P.T. Schumacker, N. Chandel, W. Seeger and J.I. Sznajder.  AMP-activated protein kinase regulates CO2-induced alveolar epithelial dysfunction in rats and human cells by promoting Na,K-ATPase endocytosis. J. Clin. Invest. 118(2):752-762, 2008.

Sharabi K., A. Hurwitz, A. Simon, G.J. Beitel, R.I. Morimoto, G. Rechavi, J.I. Sznajder and Y. Gruenbaum.  Elevated CO2 levels affects development, motility, fertility and extends lifespan in Caenorhabditis elegans.  Proc. Natl. Acad. Sci. USA. 106(10):4024-9, 2009.

Lecuona E., H. Sun, C. Vohwinkel, A. Ciechanover and J.I. Sznajder.  Ubiquitination participates in the lysosomal degradation of the Na,K-ATPase in steady state conditions.  Am. J. Respir. Cell Mol. Biol. 41(6):671-9, 2009. PMID: 19286978.

Helenius I.T, T. Krupinski, D.W. Turnbull, Y. Gruenbaum, N. Silverman, E.A. Johnson, P.H. Sporn, J.I. Sznajder and G.J. Beitel.  Elevated CO2 suppresses specific Drosophila innate immune responses downstream of NF-KB activation. Proc. Natl. Acad. Sci. USA. 106(44):18710-5, 2009.  PMID: 19846771.

Trejo H., E. Lecuona, D. Grillo, I. Szleifer, O. Nekrasova, V. Gelfand and J.I. Sznajder.  Role of kinesin light chain-2 of kinesin-1 in the trafficking of  Na,K-ATPase-containing vesicles in alveolar epithelial cells.  FASEB J. 24:374-82, 2010.  PMID: 19773350

Dada L.A. and J.I. Sznajder.  Mitochondrial Ca2+ and ROS take center stage to orchestrate TNFα-mediated inflammatory responses.  J. Clin. Invest. 121(5):1683–1685, 2011. PMID:21519140

Gusarova G., L, Dada, A. Briva, H. Trejo, R.B. Hamanka, G.M. Mutlu, N.S. Chandel, M. Prakriya and J.I. Sznajder. Hypoxia leads to Na,K-ATPase downregulation via Ca2+ release-activated Ca2+ (CRAC) channels and AMPK.  Mol. Cell. Biol. 31(17):3546-56, 2011, PMID: 21730292.

Vohwinkel C.U., E. Lecuona H. Sun, N. Sommer, I. Vadász, N.S. Chandel and J.I. Sznajder. Hypercapnia leads to mitochondrial dysfunction and decreased cell proliferation. J. Biol. Chem. E-Pub September 8, . PMID: 21903582, 2011.

Pub med

View Publications by Jacob Sznajder listed in the National Library of Medicine (PubMed).