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Alexander D Verin

Alexander D Verin

Augusta University
USA

Title: Adenosine in lung endothelial barrier strengthening: role of Rac1 and MLCP signaling

Biography

Biography: Alexander D Verin

Abstract

Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased permeability. The mechanisms that govern the highly clinically relevant process of increased EC permeability are under intense investigation. Little is known about the processes that determine barrier preservation/enhancement. Our data indicate that extracellular adenosine is able to protect and restore EC barrier in vitro and in vivo. We also demonstrated that adenosine induce activation of small GTPase, Rac 1 and this correlates with a significant attenuation of lipopolysaccharide (LPS)-induced EC permeability increase. Conversely, introduction of active Rac1 into EC strengthen EC barrier. In parallel, adenosine induces activation of myosin light chain (MLC) phosphatase (MLCP) and this also correlates with attenuation of LPS-induced EC permeability. In addition, we have shown that inhibition of MLCP leads to the phosphorylation of several cytoskeletal targets, which correlates with permeability increase suggesting that dephosphorylation of these proteins may be involved in the barrier-enhancing effect. Further, introduction of active MLCP subunits into the lung endothelium reduces LPS-induced lung inflammation strongly supporting the positive role of MLCP activity in EC barrier preservation against ALI in murine model. Therefore, the ability of adenosine to strengthen EC barrier appears to be dependent on Rac1 and MLCP activation. We speculate that adenosine-induced EC barrier preservation requires the coordinated activation of Rac1 and MLCP leading to EC cytoskeletal changes.