Digitized Honors Theses (2002-2017)

Date of Award

5-2012

Document Type

Undergraduate Thesis

Degree Name

BS

Department

Neuroscience

Faculty Mentor

Sarah Sayner

Abstract

Cytosolic pools of cAMP are destructive to the pulmonary endothelial barrier. The process through which cAMP causes gaps between pulmonary microvascular endothelial cells involves several signaling steps. Soluble, endogenous adenylyl cyclase isoform 1O is activated by bicarbonate to generate a cytosolic pool of cAMP. Cyclic AMP in turn activates protein kinase A. The microtubule associating protein, tau, is a target of protein kinase A phosphorylation. The phosphorylation of tau at serine 214 causes disruption of microtubules, and in turn, gaps between pulmonary microvascular endothelial cells. Electrical resistance recordings show bicarbonate stimulation decreases the integrity of the pulmonary microvascular endothelial barrier. Western blot analysis indicates a trending increase in tau phosphorylation at serine 214 when cells are treated with bicarbonate. Also, immunocytochemistry demonstrates bicarbonate stimulation reduces the extent of polymerized microtubules. This data suggests that bicarbonate stimulation of adenylyl cyclase 1O causes phosphorylation of tau, disruption of microtubules, and thereby an increase in permeability across of the pulmonary endothelial barrier.

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