Date of Award
Master of Science
Dr. Karel Tyml
Electrical coupling between endothelial cells of the inner surface of arterioles is required for the arteriolar conducted response that coordinates microvascular function along the vascular tree. Gap junction proteins, connexins (Cx), form inter-endothelial channels, which facilitate exchangeofmetabolitesandelectricalsignalsbetweencells. Ourlabhasreportedthat,among the connexins found in endothelial cells, Cx40 is the target protein responsible for lipopolysaccharide (LPS) - and hypoxia/reoxygenation (H/R)-induced reduction in electrical coupling between mouse microvascular endothelial cells (MMEC) was assessed. LPS is an initiating factor in sepsis and its effect could be aggravated by H/R present in septic tissue. Using electrophysiology the role of the Cx40 cytoplasmic carboxylic tail in LPS-, H/R-, and LPS+H/R- induced reduction in coupling between MMEC was assessed. LPS, H/R or LPS+H/R reduced coupling in WT cells and in Cx40 knock-out (KO) cells infected with adenovirus carrying Cx40 cDNA (AdV-Cx40). Reduction in coupling was larger after LPS+H/R than after LPS or H/R alone. No change in coupling was seen in Cx40KO cells and in Cx40KO cells infected with AdV-Cx40A237-358 (Cx40 without its cytoplasmic carboxylic tail) or with AdV-Cx4(>A345-358 (Cx40 withoutitstailtip). ItisconcludedthattheCx40tailtipiscrucialinCx40functionduring inflammatory conditions, including compromised arteriolar conducted response during sepsis.
Siddiqui, Mohammad F., "CRITICAL ROLE OF CX40 CARBOXYLIC TAIL IN REDUCED ELECTRICAL COUPLING BETWEEN MICROVASCULAR ENDOTHELIAL CELLS IN SEPSIS" (2009). Digitized Theses. 3853.