TY - JOUR
T1 - IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB
AU - Maldonado, Carola
AU - Cea, Paola
AU - Adasme, Tatiana
AU - Collao, Andrés
AU - Díaz-Araya, Guillermo
AU - Chiong, Mario
AU - Lavandero, Sergio
N1 - Funding Information:
We thank Fidel Albornoz for his technical assistance. We also thank Dr. Charles Vinson (NIH, Bethesda, USA) for his kind donation of CREB adenovirus. This work was supported by FONDECYT Grant 1010246 and FONDAP Grant 15010006 (S.L.), Beca Apoyo Tesis-and Graduate Grant UCH PG (C.M.), Sociedad de Cardiología Grant (C.M.). C.M. hold a fellowship from CONICYT, Chile.
PY - 2005/11/4
Y1 - 2005/11/4
N2 - Hyperosmotic stress stimulates a rapid and pronounced apoptosis in cardiac myocytes which is attenuated by insulin-like growth factor-1 (IGF-1). Because in these cells IGF-1 induces intracellular Ca2+ increase, we assessed whether the cyclic AMP response element-binding protein (CREB) is activated by IGF-1 through Ca2+-dependent signalling pathways. In cultured cardiac myocytes, IGF-1 induced phosphorylation (6.5 ± 1.0-fold at 5 min), nuclear translocation (30 min post-stimulus) and DNA binding activity of CREB. IGF-1-induced CREB phosphorylation was mediated by MEK1/ERK, PI3-K, p38-MAPK, as well as Ca2+/calmodulin kinase and calcineurin. Exposure of cardiac myocytes to hyperosmotic stress (sorbitol 600 mOsm) decreased IGF-1-induced CREB activation Moreover, overexpression of a dominant negative CREB abolished the anti-apoptotic effects of IGF-1. Our results suggest that IGF-1 activates CREB through a complex signalling pathway, and this transcription factor plays an important role in the anti-apoptotic action of IGF-1 in cultured cardiac myocytes.
AB - Hyperosmotic stress stimulates a rapid and pronounced apoptosis in cardiac myocytes which is attenuated by insulin-like growth factor-1 (IGF-1). Because in these cells IGF-1 induces intracellular Ca2+ increase, we assessed whether the cyclic AMP response element-binding protein (CREB) is activated by IGF-1 through Ca2+-dependent signalling pathways. In cultured cardiac myocytes, IGF-1 induced phosphorylation (6.5 ± 1.0-fold at 5 min), nuclear translocation (30 min post-stimulus) and DNA binding activity of CREB. IGF-1-induced CREB phosphorylation was mediated by MEK1/ERK, PI3-K, p38-MAPK, as well as Ca2+/calmodulin kinase and calcineurin. Exposure of cardiac myocytes to hyperosmotic stress (sorbitol 600 mOsm) decreased IGF-1-induced CREB activation Moreover, overexpression of a dominant negative CREB abolished the anti-apoptotic effects of IGF-1. Our results suggest that IGF-1 activates CREB through a complex signalling pathway, and this transcription factor plays an important role in the anti-apoptotic action of IGF-1 in cultured cardiac myocytes.
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U2 - 10.1016/j.bbrc.2005.08.245
DO - 10.1016/j.bbrc.2005.08.245
M3 - Article
C2 - 16168389
AN - SCOPUS:25644455945
SN - 0006-291X
VL - 336
SP - 1112
EP - 1118
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -