Journal of Molecular Neuroscience

, Volume 17, Issue 3, pp 285–292 | Cite as

Roles of BCL-2 and caspase 3 in the adenosine A3 receptor-induced apoptosis

  • Elena Appel
  • Gila Kazimirsky
  • Ely Ashkenazi
  • Seong Gon Kim
  • Kenneth A. Jacobson
  • Chaya Brodie
Article

Abstract

Selective A3 adenosine receptor agonists have been shown to induce apoptosis in a variety of cell types. In this study we examined the effects of adenosine receptor agonists selective for A1, A2A, or A3 receptors on the induction of apoptosis in primary cultures of rat astrocytes and in C6 glial cells. Treatment of the cells with the A3 receptor agonist Cl-IB-MECA (10 µM) induced apoptosis in both cell types. The effects of Cl-IB-MECA were partially antagonized by the A3 receptor-selective antagonist MRS 1191. In contrast, the A1 and A2A receptor agonists, CPA and CGS 21680, respectively, did not have significant effects on apoptosis in these cells. Cl-IB-MECA reduced the expression of endogenous Bcl-2, whereas it did not affect the expression of Bax. Overexpression of Bcl-2 in C6 cells abrogated the induction of apoptosis induced by the A3 agonist. Cl-IB-MECA also induced an increase in caspase 3 activity and caspase inhibitors decreased the apoptosis induced by the A3 agonist. These findings suggest that intense activation of the A3 receptor is pro-apoptotic in glial cells via bcl2 and caspase-3 dependent pathways.

Index Entries

Astrocytes agonists adenosine receptor apoptosis Bcl-2 

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Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Elena Appel
    • 1
  • Gila Kazimirsky
    • 1
  • Ely Ashkenazi
    • 2
  • Seong Gon Kim
    • 3
  • Kenneth A. Jacobson
    • 3
  • Chaya Brodie
    • 1
  1. 1.Gonda (Goldschmied) Medical Diagnosis Research Center, Faculty of Life ScienceBar-Ilan UniversityRamat GanIsrael
  2. 2.Department of NeurosurgeryHadassa HospitalJerusalemIsrael
  3. 3.Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney DiseasesNational Institutes of HealthBethesda

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