Publications

Detailed Information

Inhibition of the activity of excitatory amino acid transporter 4 expressed in Xenopus oocytes after chronic exposure to ethanol

DC Field Value Language
dc.contributor.authorYoo, Seung-Yeon-
dc.contributor.authorKim, Jin-Hee-
dc.contributor.authorDo, Sang-Hwan-
dc.contributor.authorZuo, Zhiyi-
dc.date.accessioned2010-01-27T08:44:43Z-
dc.date.available2010-01-27T08:44:43Z-
dc.date.issued2008-06-11-
dc.identifier.citationAlcohol Clin Exp Res. 2008 Jul;32(7):1292-8.en
dc.identifier.issn1530-0277 (Electronic)-
dc.identifier.issn1530-0277 (Linking)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18540911-
dc.identifier.urihttps://hdl.handle.net/10371/45522-
dc.description.abstractBACKGROUND: The extracellular glutamate concentration is tightly controlled by excitatory amino acid transporters (EAATs). EAAT4 is the predominant EAAT in the cerebellar Purkinje cells. Purkinje cells play a critical role in motor coordination and may be an important target for ethanol to cause motor impairments. We designed this study to determine the effects of chronic ethanol exposure on the activity of EAAT4 and evaluate the involvement of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in these effects. METHODS: EAAT4 was expressed in Xenopus oocytes following injection of EAAT4 mRNA. Oocytes were incubated with ethanol-containing solution for 24 to 96 hours. Membrane currents induced by l-aspartate were recorded using 2-electrode voltage clamps. Responses were quantified by integration of the current trace and reported in microCoulombs (microC). RESULTS: Ethanol dose- and time-dependently reduced EAAT4 activity. EAAT4 activity after a 96-hour exposure was significantly decreased compared to the control values at all concentrations tested (10 to 100 mM). Ethanol (50 mM) significantly decreased the Vmax (2.2 +/- 0.2 microC for control vs. 1.6 +/- 0.2 microC for ethanol, n = 18, p < 0.05) of EAAT4 for L-aspartate. Preincubation of ethanol-treated (50 mM for 96 hours) oocytes with phorbol-12-myrisate-13-acetate (100 nM for 10 minutes) abolished the ethanol-induced decrease in EAAT4 activity. While staurosporine (2 microM for 1 hour) or chelerythrine (100 microM for 1 hour) significantly decreased EAAT4 activity, no difference was observed in EAAT4 activity among the staurosporine, ethanol, or ethanol plus staurosporine groups. Similarly, EAAT4 activity did not differ among the chelerythrine, ethanol, or ethanol plus chelerythrine groups. Pretreatment of the oocytes with wortmannin (1 microM for 1 hour) also significantly decreased EAAT4 activity. However, no difference was observed in the wortmannin, ethanol, or ethanol plus wortmannin groups. CONCLUSIONS: The results of this study suggest that chronic ethanol exposure decreases EAAT4 activity and that PKC and PI3K may be involved in these effects. These effects of ethanol on EAAT4 may cause an increase in peri-Purkinje cellular glutamate concentration, and may be involved in cerebellar dysfunction and motor impairment after chronic ethanol ingestion.en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.subject1-Phosphatidylinositol 3-Kinase/*metabolismen
dc.subjectAnimalsen
dc.subjectCentral Nervous System Depressants/administration & dosage/*pharmacologyen
dc.subjectEthanol/administration & dosage/*pharmacologyen
dc.subjectExcitatory Amino Acid Transporter 4/*antagonists & inhibitors/geneticsen
dc.subjectFemaleen
dc.subjectMicroinjectionsen
dc.subjectOocytesen
dc.subjectProtein Kinase C/*metabolismen
dc.subjectRatsen
dc.subjectXenopus laevisen
dc.titleInhibition of the activity of excitatory amino acid transporter 4 expressed in Xenopus oocytes after chronic exposure to ethanolen
dc.typeArticleen
dc.contributor.AlternativeAuthor유승연-
dc.contributor.AlternativeAuthor김진희-
dc.contributor.AlternativeAuthor도상환-
dc.identifier.doi10.1111/j.1530-0277.2008.00697.x-
Appears in Collections:
Files in This Item:
There are no files associated with this item.

Altmetrics

Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Share