Volatile anesthetics affect the morphology of rat glioma C6 cells via RhoA, ERK, and Akt activation.
Treatment of rat glioma C6 cells with the beta-receptor agonist isoproterenol induces a massive increase in cAMP. Concomitantly the cells change their morphology from a fibroblast-type to an astrocyte-like (stellated) cell shape. The stellated morphology can be completely reverted by thrombin and sphingosine-1-phosphate (S-1-P) but also to a certain extent by clinical concentrations of volatile anesthetics. The anesthetic-induced reversion of the stellated cell shape seems to be mediated by a number of cellular alterations. Central to the effect is most likely a RhoA/Rho-kinase activation, but also the MAPKK/MEK and the Akt/protein kinase B pathway are activated by the anesthetics. With the use of specific inhibitors we were able to show that activation of the MAPKK/MEK pathway inhibits, whereas activation of the Akt/protein kinase B pathway stimulates the reversal of the stellated cell shape by the anesthetics. In summary, volatile anesthetics affect the morphology of rat glioma C6 cells by activation of the RhoA/Rho kinase, the MAPKK/MEK, and the Akt/protein kinase B signaling pathways.
Tas
Piet W L
PW
Department of Anaesthesiology, University of Würzburg, Center of Operative Medicine, Würzburg, Germany. tas_p@klinik.uni-wuerzburg.de
Gambaryan
Stepan
S
Roewer
Norbert
N
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D005910:Glioma; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000577:Amides; D018685:Anesthetics, Inhalation; D016895:Culture Media, Serum-Free; D005419:Flavonoids; D011725:Pyridines; C108830:Y 27632; D007530:Isoflurane; D051058:Oncogene Protein v-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020742:rhoA GTP-Binding Protein; D007545:Isoproterenol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D006221:Halothane