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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-5-27
pubmed:abstractText
Etomoxir, an inhibitor of mitochondrial carnitine palmitoyltransferase-1, is known to attenuate the changes in myosin isoforms and sarcoplasmic reticular function that occur in diabetic rat hearts. In the present study, we tested the hypothesis that etomoxir also prevents the diabetes-induced depression of sarcolemmal (SL) Na+-K+ATPase activity by differentially affecting its alpha and beta-subunit levels. Streptozotocin-induced diabetes was associated with a decreased in alpha2-, alpha3-subunit levels, whereas the alpha1-and beta1-subunits were unchanged. Treatment of diabetic rats for 4 weeks with etomoxir (8 mg/kg/day) increased the alpha1-subunit levels, but failed to prevent the decrease in alpha2- and alpha3-subunit levels. In euglycemic control rats, etomoxir increased the alpha1-subunit protein level per g heart weight, but did not alter the alpha2-, alpha3- and beta1-subunit levels. The large decrease in Na+-K+ ATPase activity per g heart weight in diabetic rats was prevented by etomoxir, which suggests that the increased alpha1-subunit levels seen with this drug compensated for the decreased alpha2- and alpha3-subunit levels. The SL yield was also increased by etomoxir in euglycemic rats in proportion to the higher alpha1-subunit level, which resulted in an unchanged alpha1-content when expressed per mg SL protein; however, the alpha2- and beta1-subunit levels were reduced (p < 0.05). The depressed alpha2- and beta3 subunit levels of diabetic rats were associated with reduced mRNA abundance. However, no increase in alpha1-subunit mRNA abundance was seen in the etomoxir treated rats, which suggests that possibly post-transcriptional mechanisms are occurring in these hearts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0300-8177
pubmed:author
pubmed:issnType
Print
pubmed:volume
232
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
57-62
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Differential effects of etomoxir treatment on cardiac Na+-K+ ATPase subunits in diabetic rats.
pubmed:affiliation
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't