Propofol reverses oxidative stress-attenuated glutamate transporter EAAT3 activity: evidence of protein kinase C involvement.
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.
Yun
Jung-Yeon
JY
Department of Anesthesiology, Research Institute and Hospital, National Cancer Center, Gyeonggi -do, and Seoul National University Hospital, South Korea.
Park
Kum-Suk
KS
Kim
Jin-Hee
JH
Do
Sang-Hwan
SH
Zuo
Zhiyi
Z
D000818:Animals; D004305:Dose-Response Relationship, Drug; D050580:Excitatory Amino Acid Transporter 3 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D015742:Propofol / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014981:Xenopus; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D050580:Excitatory Amino Acid Transporter 3; D018696:Neuroprotective Agents; C493398:Slc1a1 protein, rat; D020122:tert-Butylhydroperoxide; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D015742:Propofol