Insulin-like Growth Factor-1 Induces an Inositol 1,4,5-Trisphosphate-dependent Increase in Nuclear and Cytosolic Calcium in Cultured Rat Cardiac Myocytes

Cristian Ibarra, Manuel Estrada, Loreto Carrasco, Mario Chiong, José L. Liberona, César Cardenas, Guillermo Díaz-Araya, Enrique Jaimovich, Sergio Lavandero

Résultat de rechercheexamen par les pairs

73 Citations (Scopus)

Résumé

In the heart, insulin-like growth factor-1 (IGF-1) is a pro-hypertrophic and anti-apoptotic peptide. In cultured rat cardiomyocytes, IGF-1 induced a fast and transient increase in Ca2+i levels apparent both in the nucleus and cytosol, releasing this ion from intracellular stores through an inositol 1,4,5-trisphosphate (IP3)-dependent signaling pathway. Intracellular IP3 levels increased after IGF-1 stimulation in both the presence and absence of extracellular Ca2+. A different spatial distribution of IP3 receptor isoforms in cardiomyocytes was found. Ryanodine did not prevent the IGF-1-induced increase of Ca 2+i levels but inhibited the basal and spontaneous Ca 2+i oscillations observed when cardiac myocytes were incubated in Ca2+-containing resting media-Spatial analysis of fluorescence images of IGF-1-stimulated cardiomyocytes incubated in Ca 2+-containing resting media showed an early increase in Ca 2+i, initially localized in the nucleus. Calcium imaging suggested that part of the Ca2+ released by stimulation with IGF-1 was initially contained in the perinuclear region. The IGF-1-induced increase on Ca2+i levels was prevented by 1,2-bis(2-aminophenoxy)ethane-N,N,N′N′-tetraacetic acid-AM, thapsigargin, xestospongin C, 2-aminoethoxy diphenyl borate, U-73122, pertussis toxin, and βARKct (a peptide inhibitor of Gβγ signaling). Pertussis toxin also prevented the IGF-1-dependent IP3 mass increase. Genistein treatment largely decreased the IGF-1-induced changes in both Ca 2+i and IP3. LY29402 (but not PD98059) also prevented the IGF-1-dependent Ca2+i increase. Both pertussis toxin and U73122 prevented the IGF-1-dependent induction of both ERKs and protein kinase B. We conclude that IGF-1 increases Ca2+ i levels in cultured cardiac myocytes through a Gβγ subunit of a pertussis toxin-sensitive G protein-PI3K-phospholipase C signaling pathway that involves participation of IP3.

Langue d'origineEnglish
Pages (de-à)7554-7565
Nombre de pages12
JournalJournal of Biological Chemistry
Volume279
Numéro de publication9
DOI
Statut de publicationPublished - févr. 27 2004

ASJC Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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