Propofol reverses oxidative stress-attenuated glutamate transporter EAAT3 activity: evidence of protein kinase C involvement

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Yun, Jung-Yeon; Park, Kum-Suk; Kim, Jin-Hee; Do, Sang-Hwan; Zuo, Zhiyi
Issue Date
Eur J Pharmacol. 2007 Jun 22;565(1-3):83-8. Epub 2007 Mar 3.
AnimalsDose-Response Relationship, DrugExcitatory Amino Acid Transporter 3/*drug effects/genetics/physiologyNeuroprotective Agents/pharmacology*Oxidative StressPropofol/*pharmacologyProtein Kinase C/*physiologyRatsStaurosporine/pharmacologyTetradecanoylphorbol Acetate/pharmacologyXenopustert-Butylhydroperoxide/pharmacology
The authors investigated the effects of propofol on EAAT3 (excitatory amino acid transporter 3) activity under oxidative stress induced by tert-butyl hydroperoxide (t-BHP), and the mediation of these effects by protein kinase C (PKC). Rat EAAT3 was expressed in Xenopus oocytes and L-glutamate (30 microM)-induced membrane currents were measured using the two-electrode voltage clamp technique. Exposure of these oocytes to t-BHP (1-20 mM) for 10 min dose-dependently decreased EAAT3 activity, and t-BHP (5 mM) significantly decreased the Vmax, but not the Km of EAAT3 for glutamate, and propofol (1-100 microM) dose-dependently reversed this t-BHP-attenuated EAAT3 activity. Phorbol-12-myristate-13-acetate (a PKC activator), also abolished this t-BHP-induced reduction in EAAT3 activity, whereas staurosporine (a PKC inhibitor), significantly decreased EAAT3 activity. However, as compared with staurosporine or t-BHP alone, t-BHP and staurosporine in combination did not further reduce EAAT3 activity. A similar pattern was observed for chelerythrine (also a PKC inhibitor). In oocytes pretreated with combinations of t-BHP and PMA (or staurosporine), propofol failed to change EAAT3 activity. Our results suggest that propofol restores oxidative stress-reduced EAAT3 activity and that these effects of propofol may be PKC-mediated.
0014-2999 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Anesthesiology and Pain Medicine (마취통증의학전공)Journal Papers (저널논문_마취통증의학전공)
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