Show simple item record

A Mechanism for Altered Polyunsaturated Fatty Acid Biosynthesis in Cystic Fibrosis

dc.creatorUmunakwe, Obinna C.
dc.date.accessioned2020-08-22T20:31:55Z
dc.date.available2016-08-04
dc.date.issued2014-08-04
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-07222014-114609
dc.identifier.urihttp://hdl.handle.net/1803/13452
dc.description.abstractCystic fibrosis (CF) is a debilitating, multi-organ, autosomal recessive disease caused by mutations leading to absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) in epithelial cells. Chronic pulmonary disease, characterized by excessive inflammation and recurrent infections, is the primary source of morbidity and mortality in individuals with CF. Altered polyunsaturated fatty acid (PUFA) biosynthesis, resulting in increased metabolism of linoleic acid (LA) to arachidonic acid (AA), plays a key role in CF pathophysiology. Increased AA biosynthesis contributes to excessive inflammation in the lungs of individuals with CF. The mechanism by which absence of functional CFTR leads to aberrant PUFA biosynthesis has been elusive. This dissertation is the first delineation of a pathway linking PUFA metabolism to CFTR. Through studies in human bronchial epithelial cells, this dissertation demonstrates that absence of functional CFTR leads to increased activation of AMP-activated protein kinase (AMPK) by calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ). Elevated AMPK activity leads to increased expression and activity of Δ6-desaturase (Δ6D) and Δ5-desaturase (Δ5D). Increased activity of Δ6D and Δ5D results in increased metabolism of LA to AA.
dc.format.mimetypeapplication/pdf
dc.subjectdesaturase
dc.subjectarachidonic acid
dc.subjectlinoleic acid
dc.subjectAMP-activated protein kinase
dc.titleA Mechanism for Altered Polyunsaturated Fatty Acid Biosynthesis in Cystic Fibrosis
dc.typedissertation
dc.contributor.committeeMemberTimothy S. Blackwell
dc.contributor.committeeMemberW. Gray Jerome
dc.contributor.committeeMemberP. Anthony Weil
dc.contributor.committeeMemberMichael Laposata
dc.contributor.committeeMemberAdam C. Seegmiller
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplinePathology
thesis.degree.grantorVanderbilt University
local.embargo.terms2016-08-04
local.embargo.lift2016-08-04
dc.contributor.committeeChairLarry L. Swift


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record