Linked Life Data

12967637

Source:http://linkedlifedata.com/resource/pubmed/id/12967637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-9-11
pubmed:abstractText
Reduced glutathione (GSH) is an essential, multifunctional tripepetide that controls redox-sensitive cellular processes, but its regulation in the heart is poorly understood. The present study used a pharmocological model of GSH depletion to examine cellular mechanisms controlling cardiac GSH. Inhibition of GSH metabolism was elicited in normal rats by daily injections of buthionine sulfoximine (BSO), a blocker of gamma-glutamylcysteine synthetase, plus 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase. After 3 d of BSO/BCNU treatment, intracellular [GSH] was measured in isolated-ventricular myocytes by fluorescence microscopy using the probe monochlorobimane. Basal [GSH] in left-ventricular myocytes from BSO/BCNU-treated rats (2.0 +/- 0.05 amol/microm(3), n = 146) was 50% less than control (4.0 +/- 0.13 amol/microm(3), n = 116; P < 0.05). Incubation of myocytes from BSO/BCNU rats with 0.1 microM insulin normalized [GSH] after a delay of 3-4 h (3.6 +/- 0.29 amol/microm(3), n = 66). This effect of insulin was blocked by pre-treating myocytes with cycloheximide. A protein tyrosine phosphatase inhibitor, bis-peroxovanadium-1,10-phenanthroline (bpV(phen), 1 microM), elicited a similar effect as insulin, while neither agent altered [GSH] in myocytes from control rats. Moreover, the effect of insulin and bpV(phen) to up-regulate GSH was blocked by inhibitors of PI 3-kinase (wortmannin, LY294002), MEK (PD98059) and p38 MAP kinases (SB203580). These data suggest that the insulin-signaling cascade regulates [GSH] in ventricular myocytes by a coordinated activation of PI 3-kinase and MAP kinase pathways. These signaling mechanisms may play essential roles in controlling intracellular redox state and normal function of cardiac myocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1145-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12967637-Animals, pubmed-meshheading:12967637-Antineoplastic Agents, Alkylating, pubmed-meshheading:12967637-Blood Pressure, pubmed-meshheading:12967637-Buthionine Sulfoximine, pubmed-meshheading:12967637-Carmustine, pubmed-meshheading:12967637-Drug Interactions, pubmed-meshheading:12967637-Enzyme Inhibitors, pubmed-meshheading:12967637-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12967637-Glutamate-Cysteine Ligase, pubmed-meshheading:12967637-Glutathione, pubmed-meshheading:12967637-Glutathione Reductase, pubmed-meshheading:12967637-Heart Rate, pubmed-meshheading:12967637-Heart Ventricles, pubmed-meshheading:12967637-Male, pubmed-meshheading:12967637-Myocytes, Cardiac, pubmed-meshheading:12967637-Rats, pubmed-meshheading:12967637-Rats, Sprague-Dawley, pubmed-meshheading:12967637-Time Factors
pubmed:year
2003
pubmed:articleTitle
Regulation of glutathione in cardiac myocytes.
pubmed:affiliation
Department of Physiology and Biophysics, University of Nebraska College of Medicine, 984575 Nebraska Medical Center, Omaha, NE 68198-4575, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't