TY - JOUR
T1 - The A3 adenosine receptor mediates cell spreading, reorganization of actin cytoskeleton, and distribution of Bcl-x(L)
T2 - Studies in human astroglioma cells
AU - Abbracchio, Maria P.
AU - Rainaidi, Gabriella
AU - Giammarioli, Anna Maria
AU - Ceruti, Stefania
AU - Brambilla, Roberta
AU - Cattabeni, Flaminio
AU - Barbieri, Daniela
AU - Franceschi, Claudio
AU - Jacobson, Kenneth A.
AU - Malorni, Walter
N1 - Funding Information:
This work was partially supported by National Research Council (CNR) grants n° 96.04972.St74 to Daniela Monti and n° 96.04967.St74 to WM, by a grant of the Associazione Italiana per la Ricerca sul Cancro (AIRC) to CF, and by The Italian Ministero dell'Universita' e Ricerca Scienti®ca e Tecnologica (40% to MPA, FC and CF). M.P.A., S.C., R.B. and F.C. have been involved in the concerted action ADEURO (EU, BIOMED1, ``Physiology and pharmacology of brain adenosine receptors-implications for the rational design of neuroactive drugs'' supported by the European Union within the Biomedical and Health Research Programme). Cl-IB-MECA was kindly provided by Research Biochemical International as part of the Chemical Synthesis Program of the National Institute of Mental Health, Contract N°01MH30003.
PY - 1997/12/18
Y1 - 1997/12/18
N2 - The pathophysiological role of the adenosine A3 receptor in the central nervous system is largely unknown. We have investigated the effects of the selective A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine, CI-IB-MECA, in cells of the astroglial lineage (human astrocytoma ADF cells). A marked reorganization of the cytoskeleton, with appearance of stress fibers and numerous cell protrusions, was found following exposure of cells to low (nM) concentrations of CI-IB-MECA. These 'trophic' effects were accompanied by induction of the expression of Rho, a small GTP-binding protein, which was virtually absent in control cells, and by changes of the intracellular distribution of the antiapoptotic protein Bcl-x(L), that, in agonist-exposed cells, became specifically associated to cell protrusions. This is the first demonstration that the intracellular organization of Bcl-x(L) can be modulated by the activation of a G-protein-coupled membrane receptor, such as the A3 adenosine receptor. Moreover, modulation of the astrocytic cytoskeleton by adenosine may have intriguing implications in both nervous system development and in the response of the brain to trauma and ischemia.
AB - The pathophysiological role of the adenosine A3 receptor in the central nervous system is largely unknown. We have investigated the effects of the selective A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine, CI-IB-MECA, in cells of the astroglial lineage (human astrocytoma ADF cells). A marked reorganization of the cytoskeleton, with appearance of stress fibers and numerous cell protrusions, was found following exposure of cells to low (nM) concentrations of CI-IB-MECA. These 'trophic' effects were accompanied by induction of the expression of Rho, a small GTP-binding protein, which was virtually absent in control cells, and by changes of the intracellular distribution of the antiapoptotic protein Bcl-x(L), that, in agonist-exposed cells, became specifically associated to cell protrusions. This is the first demonstration that the intracellular organization of Bcl-x(L) can be modulated by the activation of a G-protein-coupled membrane receptor, such as the A3 adenosine receptor. Moreover, modulation of the astrocytic cytoskeleton by adenosine may have intriguing implications in both nervous system development and in the response of the brain to trauma and ischemia.
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U2 - 10.1006/bbrc.1997.7705
DO - 10.1006/bbrc.1997.7705
M3 - Article
C2 - 9425266
AN - SCOPUS:0031577677
VL - 241
SP - 297
EP - 304
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -