MCP-1/CCL2 protects cardiac myocytes from hypoxia-induced apoptosis by a Gαi-independent pathway

Sima T. Tarzami, Tina M. Calderon, Arnel Deguzman, Lillie Lopez, Richard N. Kitsis, Joan W. Berman

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Chemokines, in addition to their chemotactic properties, act upon resident cells within a tissue and mediate other cellular functions. In a previous study, we demonstrated that CCL2 protects cultured mouse neonatal cardiac myocytes from hypoxia-induced cell death. Leukocyte chemotaxis has been shown to contribute to ischemic injury. While the chemoattractant properties of CCL2 have been established, the protective effects of this chemokine suggest a novel role for CCL2 in myocardial ischemia/reperfusion injury. The present study examined the cellular signaling pathways that promote this protection. Treatment of cardiac myocyte cultures with CCL2 protected them from hypoxia-induced apoptosis. This protection was not mediated through the activation of G αi signaling that mediates monocyte chemotaxis. Inhibition of the ERK1/2 signaling pathway abrogated CCL2 protection. Caspase 3 activation and JNK/SAPK phosphorylation were decreased in hypoxic myocytes co-treated with CCL2 as compared to hypoxia only-treated cultures. Expression of the Bcl-2 family proteins, Bcl-xL and Bag-1, was increased in CCL2-treated myocytes subjected to hypoxia. There was also downregulation of Bax protein levels as a result of CCL2 co-treatment. These data suggest that CCL2 cytoprotection and chemotaxis may occur through distinct signaling mechanisms.

Original languageEnglish (US)
Pages (from-to)1008-1016
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume335
Issue number4
DOIs
StatePublished - Oct 7 2005

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Keywords

  • Apoptosis
  • Bcl-2
  • Caspases
  • ERK1/2
  • G proteins
  • Hypoxia
  • JNK/SAPK
  • MCP-1/CCL2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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