Insulin-like growth factor-1 protects H9c2 cardiac myoblasts from oxidative stress-induced apoptosis via phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways

Feng Hong, Si Joong Kwon, Bong Sook Jhun, Sung Soo Kim, Joohun Ha, Soo Ja Kim, Nak Won Sohn, Chulhun Kang, Insug Kang

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Oxidative stress plays a critical role in cardiac injuries during ischemia/reperfusion. Insulin-like growth factor-1 (IGF-1) promotes cell survival in a number of cell types, but the effect of IGF-1 on the oxidative stress has not been elucidated in cardiac muscle cells. Therefore, we examined the role of IGF-1 signaling pathway in cell survival against H2O2-induced apoptosis in H9c2 cardiac myoblasts. H2O2 treatment induced apoptosis in H9c2 cells, and pretreatment of cells with IGF-1 suppressed apoptotic cell death. The antiapoptotic effect of IGF-1 was blocked by LY294002 (an inhibitor of phosphatidylinositol 3-kinase) and by PD98059 (an inhibitor of extracellular signal-regulated kinase (ERK)). The protective effect of IGF-1 was also blocked by rapamycin (an inhibitor of p70 S6 kinase). Furthermore, H9c2 cells stably transfected with constitutively active PI 3-kinase (H9c2-p110*) and Akt (H9c2-Gag-Akt) constructs were more resistant to H2O2 cytotoxicity than control cells. Although H2O2 activates both p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), IGF-1 inhibited only JNK activation. Activated PI 3-kinase (H9c2-p110*) and pretreatment of cells with IGF-1 down-regulated Bax protein levels compared to control cells. Taken together, our results suggest that IGF-1 transmits a survival signal against oxidative stress-induced apoptosis in H9c2 cells via PI 3-kinase and ERK-dependent pathways and the protective effect of IGF-1 is associated with the inhibition of JNK activation and Bax expression.

Original languageEnglish (US)
Pages (from-to)1095-1105
Number of pages11
JournalLife Sciences
Volume68
Issue number10
DOIs
StatePublished - Jan 26 2001
Externally publishedYes

Bibliographical note

Funding Information:
We are very grateful to Dr. Julian Downward at Imperial Cancer Research Fund Laboratory, United Kingdom, for providing us vectors encoding constitutively active PI 3-kinase (pcDNA3-p110*) and Akt (pSG5-Gag-Akt) used in these experiments. This work was supported by grants from Korean Ministry of Health (99-M-08-0004) and from Korea Science and Engineering Foundation (1999-2-207-008-3).

Keywords

  • Bax expression
  • H9c2 cardiac myoblasts
  • Insulin-like growth factor-1 protection
  • Oxidative stress-induced apoptosis
  • Phosphatidylinositol 3-kinase and extracellular signal-regulated kinase
  • c-jun-N-terminal kinase

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