Linked Life Data

2532015

Source:http://linkedlifedata.com/resource/pubmed/id/2532015

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1990-1-24
pubmed:abstractText
The interaction of cyclopiazonic acid with rat skeletal muscle sarcoplasmic reticulum (SR) vesicles was investigated in order to study the mechanism of cyclopiazonic acid inhibition of the Ca2+-ATPase (Goeger et al., Biochem Pharmacol 37: 978-981, 1988). Cyclopiazonic acid at 25 microM prevented the binding of Ca2+ to the high affinity binding site of mixed (light and heavy) SR vesicles and inhibited, in a dose-dependent manner, the Ca2+-dependent phosphorylation of SR vesicles by ATP. Binding of Ca2+ to the high affinity site of the CA2+-ATPase is necessary for both Ca2+ transport and for phosphorylation of the Ca2+-ATPase. We conclude that inhibition of Ca2+ binding to the high affinity site may be responsible, at least in part, for the activity of cyclopiazonic acid. The mechanism of inhibition remains unclear. The inhibition was not reduced after dialysis and was only partially reversed by gel filtration of SR vesicles treated with cyclopiazonic acid. Neither 1 mM glutathione nor dithiothreitol pretreatment had any effect on the inhibition of the Ca2+-ATPase. In addition to its inhibition of Ca2+ uptake and the Ca2+-ATPase, cyclopiazonic acid had significant effects on Ca2+ efflux from both passively and actively loaded SR vesicles. Cyclopiazonic acid impeded the efflux of Ca2+ from passively loaded SR vesicles (in the presence of ruthenium red) when compared to either untreated vesicles or those treated with mersalyl acid, a mercurial which also inhibits the Ca2+-ATPase and is known to induce Ca2+ release by both ruthenium red-sensitive and -insensitive pathways. Treatment of actively loaded vesicles with cyclopiazonic acid resulted in a decreased rate of Ca2+ efflux when compared to SR vesicles in which the Ca2+-ATPase activity was inhibited by ATP depletion with hexokinase and glucose. The results are consistent with the hypothesis that, in mixed SR vesicles, cyclopiazonic acid inhibits both the Ca2+ pump and Ca2+ efflux.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3995-4003
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Interaction of cyclopiazonic acid with rat skeletal muscle sarcoplasmic reticulum vesicles. Effect on Ca2+ binding and Ca2+ permeability.
pubmed:affiliation
U.S. Department of Agriculture, Toxicology and Mycotoxin Research Unit, Athens, GA 30613.
pubmed:publicationType
Journal Article, Comparative Study