Linked Life Data

12970367

Source:http://linkedlifedata.com/resource/pubmed/id/12970367

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2003-11-10
pubmed:abstractText
We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. Declined myocardial protection is a major feature of diabetic cardiomyopathy. These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45492-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12970367-Adenoviridae, pubmed-meshheading:12970367-Animals, pubmed-meshheading:12970367-Animals, Newborn, pubmed-meshheading:12970367-Cell Survival, pubmed-meshheading:12970367-Cells, Cultured, pubmed-meshheading:12970367-Chaperonin 10, pubmed-meshheading:12970367-Chaperonin 60, pubmed-meshheading:12970367-Cycloheximide, pubmed-meshheading:12970367-Diabetes Mellitus, Experimental, pubmed-meshheading:12970367-Genetic Vectors, pubmed-meshheading:12970367-Myocardium, pubmed-meshheading:12970367-Oligonucleotides, Antisense, pubmed-meshheading:12970367-Phosphorylation, pubmed-meshheading:12970367-Protein Processing, Post-Translational, pubmed-meshheading:12970367-Protein Synthesis Inhibitors, pubmed-meshheading:12970367-RNA, Messenger, pubmed-meshheading:12970367-Rats, pubmed-meshheading:12970367-Rats, Sprague-Dawley, pubmed-meshheading:12970367-Receptor, IGF Type 1, pubmed-meshheading:12970367-Signal Transduction, pubmed-meshheading:12970367-Time Factors, pubmed-meshheading:12970367-Ubiquitin
pubmed:year
2003
pubmed:articleTitle
Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy.
pubmed:affiliation
Department of Medicine, Biological Chemistry, Physiology and Biophysics, Center for Cardiovascular Hormone Research, University of California, Irvine, California 92697, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.