RGD Reference Report - Insulin-like growth factor binding protein-3 mediates serum starvation- and doxorubicin-induced apoptosis in H9c2 cardiac cells. - Rat Genome Database

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Insulin-like growth factor binding protein-3 mediates serum starvation- and doxorubicin-induced apoptosis in H9c2 cardiac cells.

Authors: Granata, R  De Petrini, M  Trovato, L  Ponti, R  Pons, N  Ghe, C  Graziani, A  Ferry RJ, JR  Muccioli, G  Ghigo, E 
Citation: Granata R, etal., J Endocrinol Invest. 2003 Dec;26(12):1231-41.
RGD ID: 10402811
Pubmed: PMID:15055478   (View Abstract at PubMed)
DOI: DOI:10.1007/BF03349163   (Journal Full-text)

Insulin-like growth factor binding protein 3 (IGFBP-3) modulates the activity of IGF-I, which exerts antiapoptotic action upon the myocardiocyte. IGFBP-3 also exerts IGF-independent actions to inhibit cell growth and induce apoptosis, mediating the effects of several antiproliferative agents. We hypothesized that IGFBP-3 mediates cardiomyocyte apoptosis. IGFBP-3 expression was studied in H9c2 rat cardiac cells cultured in serum-deprived medium in the absence or presence of 1 microM doxorubicin during a 72 h time-span. To a greater degree than serum withdrawal, doxorubicin induced IGFBP-3 up-regulation that was time-dependent. IGFBP-3 mRNA levels positively correlated with the degree of apoptosis. Exogenous IGFBP-3 decreased cell viability and induced apoptosis in serum-starved cells exposed to doxorubicin. IGFBP-3 antisense oligonucleotides markedly decreased apoptosis induced by either serum withdrawal or doxorubicin. Binding studies revealed specific high-affinity sites for IGFBP-3 in H9c2 cardiomyocytes, with binding characteristics typical of receptor-ligand interactions. These findings indicate that IGFBP-3 could play proapoptotic action at the myocardial level and suggest a novel role for this protein in cardiovascular dysfunction.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Igfbp3Ratpositive regulation of cardiac muscle cell apoptotic process  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igfbp3  (insulin-like growth factor binding protein 3)


Additional Information