IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB

Carola Maldonado; Paola Cea; Tatiana Adasme; Andrés Collao; Guillermo Díaz-Araya; Mario Chiong; Sergio Lavandero

doi:10.1016/j.bbrc.2005.08.245

IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB

Carola Maldonado, Paola Cea, Tatiana Adasme, Andrés Collao, Guillermo Díaz-Araya, Mario Chiong, Sergio Lavandero

Universidad de Chile

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1112-1118
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	336
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2005.08.245
Publication status	Published - Nov 4 2005

Bibliographical note

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.

Funding

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.

Funders	Funder number
Comisión Nacional de Investigación Científica y Tecnológica
Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica	1010246
Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias	15010006

ASJC Scopus Subject Areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2005.08.245

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title = "IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB",

abstract = "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.",

author = "Carola Maldonado and Paola Cea and Tatiana Adasme and Andr{\'e}s Collao and Guillermo D{\'i}az-Araya and Mario Chiong and Sergio Lavandero",

note = "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 Cardiolog{\'i}a Grant (C.M.). C.M. hold a fellowship from CONICYT, Chile.",

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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

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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.

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IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

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