Item – Theses Canada

​
OCLC number
1032960227
Link(s) to full text
LAC copy
LAC copy
Author
Yu, Hanpo.
Title
Role of Cystic Fibrosis Transmembrane Conductance Regulator and Sphingolipids in Hypoxic Pulmonary Vasoconstriction.
Degree
(MAST)--University of Toronto, 2012.
Publisher
Toronto : University of Toronto, 2012.
Description
1 online resource
Notes
Includes bibliographical references.
Abstract
Hypoxic pulmonary vasoconstriction (HPV) optimizes ventilation-perfusion matching in the lung. As cystic fibrosis patients suffer from ventilation-perfusion mismatches, we probe for a potential role for cystic fibrosis transmembrane conductance regulator (CFTR) in HPV. HPV in isolated mouse lungs is attenuated by CFTR inhibition or deficiency. In cultured human pulmonary artery smooth muscle cells (PASMC), CFTR inhibition blocks the hypoxia-induced [Ca2+ ]i increase and the caveolar translocation of transient receptor potential canonical 6 (TRPC6) channels. We also identify novel roles for sphingolipids in HPV. Ceramide production by neutral sphingomyelinase (nSMase) is required for TRPC6 translocation, and sphingosine-1-phosphste (S1P) signalling through S1P receptor 2 activates caveolae-associated TRPC6. Yet pulmonary vasoconstriction and TRPC6 translocation in response to exogenous nSMase are blocked by CFTR inhibition. CFTR function is likely required for TRPC6 trafficking or membrane stabilization, as CFTR associates with TRPC6 during hypoxia, which can be disrupted by CFTR inhibitor.
Other link(s)
tspace.library.utoronto.ca
hdl.handle.net
Subject
Hypoxic pulmonary vasoconstriction.
CFTR.
sphingolipids.
TRPC6.