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The A 3 Adenosine Receptor Induces Cytoskeleton Rearrangement in Human Astrocytoma Cells via a Specific Action on Rho Proteins
Author(s) -
ABBRACCHIO MARIA P.,
CAMURRI ALESSANDRA,
CERUTI STEFANIA,
CATTABENI FLAMINIO,
FALZANO LOREDANA,
GIAMMARIOLI ANNA MARIA,
JACOBSON KENNETH A.,
TRINCAVELLI LETIZIA,
MARTINI CLAUDIA,
MALORNI WALTER,
FIORENTINI CARLA
Publication year - 2001
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2001.tb03613.x
Subject(s) - cytoskeleton , actin cytoskeleton , adenosine , microbiology and biotechnology , agonist , actin , receptor , adenosine receptor , cofilin , chemistry , biology , biochemistry , cell
A bstract : In previous studies, we have demonstrated that exposure of astroglial cells to A 3 adenosine receptor agonists results in dual actions on cell survival, with “trophic” and antiapoptotic effects at nanomolar concentrations and induction of cell death at micromolar agonist concentrations. The protective actions of A 3 agonists have been associated with a reinforcement of the actin cytoskeleton, which likely results in increased resistance of cells to cytotoxic stimuli. The molecular mechanisms at the basis of this effect and the signalling pathway(s) linking the A 3 receptor to the actin cytoskeleton have never been elucidated. Based on previous literature data suggesting that the actin cytoskeleton is controlled by small GTP‐binding proteins of the Rho family, in the study reported here we investigated the involvement of these proteins in the effects induced by A 3 agonists on human astrocytoma ADF cells. The presence of the A 3 adenosine receptor in these cells has been confirmed by immunoblotting analysis. As expected, exposure of human astrocytoma ADF cells to nanomolar concentrations of the selective A 3 agonist 2‐chloro‐N 6 ‐(3‐iodobenzyl)‐adenosine‐5′‐ N ‐methyluronamide (Cl‐IB‐MECA) resulted in formation of thick actin positive stress fibers. Preexposure of cells to the C3B toxin that inactivates Rho‐proteins completely prevented the actin changes induced by Cl‐IB‐MECA. Exposure to the A 3 agonist also resulted in significant reduction of Rho‐GDI, an inhibitory protein known to maintain Rho proteins in their inactive state, suggesting a potentiation of Rho‐mediated effects. This effect was fully counteracted by the concomitant exposure to the selective A 3 receptor antagonist MRS1191. These results suggest that the reinforcement of the actin cytoskeleton induced by A 3 receptor agonists is mediated by an interference with the activation/inactivation cycle of Rho proteins, which may, therefore, represent a biological target for the identification of novel neuroprotective strategies.