Linked Life Data

17272355

Source:http://linkedlifedata.com/resource/pubmed/id/17272355

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-4-30
pubmed:abstractText
The role of the calpain proteases in skeletal muscle atrophy is poorly understood. One goal of these experiments was to clarify whether calpains act upstream of the ubiquitin-proteasome pathway (UPP). Calpain activation may also inhibit the anabolic signalling of Akt, since a molecular chaperone previously shown to mediate Akt activity, heat shock protein 90 (HSP 90), is a calpain substrate. Thus, an additional objective was to determine whether calpain activation affects the Akt signalling pathway. Ex vivo experiments were conducted using isolated rat diaphragm muscle. Calpain activation increased total protein degradation by 65%. Proteasome inhibition prevented this large rise in proteolysis, demonstrating that the proteasome was necessary for calpain-activated protein degradation. In addition, calpain activation increased proteasome-dependent proteolysis by 144%, further supporting the idea of sequential proteolytic pathways. Calpain reduced Akt and mammalian target of rapamycin (mTOR) phosphorylation by 35 and 50%, respectively, and activated glycogen synthase kinase-3 beta (GSK-3beta) by 40%. Additionally, calpain activation reduced HSP 90beta and mTOR protein content by 33 and 50%, respectively. These data suggest that calpains play a dual role in protein metabolism by concomitantly activating proteasome-dependent proteolysis and inhibiting the Akt pathway of protein synthesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0958-0670
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
561-73
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Calpain activation causes a proteasome-dependent increase in protein degradation and inhibits the Akt signalling pathway in rat diaphragm muscle.
pubmed:affiliation
Muscle Physiology Laboratory, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA. ira4@duke.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural