Linked Life Data

15794660

Source:http://linkedlifedata.com/resource/pubmed/id/15794660

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2005-3-29
pubmed:abstractText
Diabetic cardiomyopathy is the result of maladaptive changes in energy homeostasis. However, the biochemical mechanisms underlying dysfunctional lipid metabolism in diabetic myocardium are incompletely understood. Herein, we exploit shotgun lipidomics to demonstrate a 4-fold increase in acylcarnitines in diabetic myocardium, which was reversible upon insulin treatment. Analysis of acylcarnitine molecular species in myocardium unexpectedly identified acylcarnitine molecular species containing a mass shift of 16 amu in comparison to the anticipated molecular species. Synthesis of 3-hydroxy acylcarnitine identified the natural products as the 3-hydroxylated acylcarnitines through comparisons of diagnostic fragmentation patterns of synthetic and naturally occurring constituents using tandem mass spectrometry. Diabetes induced an increase of both calcium-independent phospholipase A(2) (iPLA(2)) mRNA and iPLA(2) activity in rat myocardium. Cardiac ischemia in myocardium genetically engineered to overexpress iPLA(2) dramatically increased the amount of acylcarnitine present in myocardium. Moreover, mechanism-based inactivation of iPLA(2) in either wild-type or transgenic myocardium ablated a substantial portion of the acylcarnitine increase. Collectively, these results identify discrete insulin remediable abnormalities in mitochondrial fatty acid processing in diabetic myocardium and identify iPLA(2) as an important enzymatic contributor to the pool of fatty acids that can be used for acylcarnitine synthesis and energy production in myocardium.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5234-45
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15794660-Animals, pubmed-meshheading:15794660-Base Sequence, pubmed-meshheading:15794660-Cardiomyopathies, pubmed-meshheading:15794660-Carnitine, pubmed-meshheading:15794660-Cricetinae, pubmed-meshheading:15794660-DNA, pubmed-meshheading:15794660-Diabetes Mellitus, Experimental, pubmed-meshheading:15794660-Group VI Phospholipases A2, pubmed-meshheading:15794660-Hydroxylation, pubmed-meshheading:15794660-Insulin, pubmed-meshheading:15794660-Male, pubmed-meshheading:15794660-Mice, pubmed-meshheading:15794660-Mice, Transgenic, pubmed-meshheading:15794660-Myocardial Ischemia, pubmed-meshheading:15794660-Myocardium, pubmed-meshheading:15794660-Phospholipases A, pubmed-meshheading:15794660-RNA, Messenger, pubmed-meshheading:15794660-Rats, pubmed-meshheading:15794660-Rats, Sprague-Dawley, pubmed-meshheading:15794660-Spectrometry, Mass, Electrospray Ionization
pubmed:year
2005
pubmed:articleTitle
Accumulation of long-chain acylcarnitine and 3-hydroxy acylcarnitine molecular species in diabetic myocardium: identification of alterations in mitochondrial fatty acid processing in diabetic myocardium by shotgun lipidomics.
pubmed:affiliation
Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.