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Propofol reverses oxidative stress-attenuated glutamate transporter EAAT3 activity: evidence of protein kinase C involvement
Cited 13 time in
Web of Science
Cited 15 time in Scopus
- Authors
- Issue Date
- 2007-03-27
- Publisher
- Elsevier
- Citation
- Eur J Pharmacol. 2007 Jun 22;565(1-3):83-8. Epub 2007 Mar 3.
- Keywords
- Animals ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Transporter 3/*drug effects/genetics/physiology ; Neuroprotective Agents/pharmacology ; Propofol/*pharmacology ; Protein Kinase C/*physiology ; Rats ; Staurosporine/pharmacology ; Tetradecanoylphorbol Acetate/pharmacology ; Xenopus ; tert-Butylhydroperoxide/pharmacology ; Oxidative Stress
- Abstract
- 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.
- ISSN
- 0014-2999 (Print)
- Language
- English
- URI
- http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1J-4N5TNBT-6&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=79300f490206700a8fb1b3e50da73919
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17382927
https://hdl.handle.net/10371/24236
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