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

doi:10.1385/JMN:17:3:285

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

The Mina and Everard Goodman Faculty of Life Sciences

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

39 Scopus citations

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, A_2A, 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 A_2A 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. CMB-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.

Original language	English
Pages (from-to)	285-292
Number of pages	8
Journal	Journal of Molecular Neuroscience
Volume	17
Issue number	3
DOIs	https://doi.org/10.1385/JMN:17:3:285
State	Published - Dec 2001

Bibliographical note

Funding Information:
1Gonda (Goldschmied) Medical Diagnosis Research Center, Faculty of Life Science, Bar-Ilan University, Ramat Gan, Israel 52900; 2Department of Neurosurgery, Hadassa Hospital, Jerusalem, Israel; and 3Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810

Funding

1Gonda (Goldschmied) Medical Diagnosis Research Center, Faculty of Life Science, Bar-Ilan University, Ramat Gan, Israel 52900; 2Department of Neurosurgery, Hadassa Hospital, Jerusalem, Israel; and 3Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810

Funders	Funder number
National Institute of Diabetes and Digestive and Kidney Diseases	Z01DK031117

Keywords

Adenosine receptor
Agonists
Apoptosis
Astrocytes
Bcl-2

Access to Document

10.1385/JMN:17:3:285

Cite this

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title = "Roles of Bcl-2 and caspase 3 in the adenosine A3 receptor-induced apoptosis",

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. CMB-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.",

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note = "Funding Information: 1Gonda (Goldschmied) Medical Diagnosis Research Center, Faculty of Life Science, Bar-Ilan University, Ramat Gan, Israel 52900; 2Department of Neurosurgery, Hadassa Hospital, Jerusalem, Israel; and 3Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810",

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AU - Jacobson, Kenneth A.

AU - Brodie, Chaya

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