Anesth Pain Med.  2011 Jul;6(3):225-230.

Effect of propofol on oxidative stress-attenuated glutamate transporter EAAT4 activity

• Ryu JH
• Kim CS
• Do SH
• Park HS

Abstract

BACKGROUND
Propofol (2, 6-diisopropylphenol) has been known to have neuroprotective effects. Excitatory amino acid transporter 4 (EAAT4) is a glutamate transporter predominantly expressed in the cerebellar Purkinje cells, which is vulnerable to ischemic injury. Thus, we hypothesized that propofol reverses reduced EAAT4 activity which was induced by oxidative stress and investigated the effects of propofol on EAAT4 under oxidative stress induced by tert-butyl hydroperoside (t-BHP).
METHODS
EAAT4 was expressed in Xenopus oocytes by injection of its mRNA. By using two-electrode voltage clamping, membrane currents were recorded before, during, and after application of L-aspartate (3 microM) in the presence or absence of t-BHP and propofol.
RESULTS
L-aspartate induced an inward current in EAAT4 expressing oocytes. Exposure of these oocytes to t-BHP (1-20 mM) for 10 min dose-dependently decreased EAAT4 activity (1 +/- 0.01 microC for control; 0.88 +/- 0.05 microC for 1 mM; 0.83 +/- 0.03 microC for 2mM; 0.65 +/- 0.04 microC for 3 mM; 0.51 +/- 0.07 microC for 5 mM; 0.45 +/- 0.03 f microC for 10 mM and 0.24 +/- 0.06 microC for 20 mM). IC50 for t-BTH was 6.05 mM and further study was performed with 10 mM t-BTH. Propofol (3-10 microM) dose-dependently reversed this t-BHP-attenuated EAAT4 activity.
CONCLUSIONS
Oxidative stress by t-BHP decreased EAAT4 activity and 3-10 microM propofol restored oxidative stress-reduced EAAT4 activity.

Keyword

Excitatory amino acid transporter 4; Glutamate transporter; Propofol; Tert-butyl hydroperoside; Xenopus oocytes

MeSH Terms

Amino Acid Transport System X-AG
Aspartic Acid
Constriction
Excitatory Amino Acid Transporter 4
Glutamic Acid
Inhibitory Concentration 50
Membranes
Neuroprotective Agents
Oocytes
Oxidative Stress
Propofol
Purkinje Cells
RNA, Messenger
Xenopus
Amino Acid Transport System X-AG
Aspartic Acid
Excitatory Amino Acid Transporter 4
Glutamic Acid
Neuroprotective Agents
Propofol
RNA, Messenger