HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 29, 26929-26937, July 18, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/29/26929    most recent M300401200v2 M300401200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, J. Articles by de la Monte, S. Search for Related Content PubMed PubMed Citation Articles by Xu, J. Articles by de la Monte, S. Social Bookmarking                      What's this?

Ethanol Impairs Insulin-stimulated Neuronal Survival in the Developing Brain

ROLE OF PTEN PHOSPHATASE^*

Julia Xu, Jong Eun Yeon, Howard Chang, Geoffrey Tison, Guo Jun Chen, Jack Wands and Suzanne de la Monte 

From the Departments of Medicine and Pathology, Rhode Island Hospital, Brown Medical School, Providence, Rhode Island 02903

Gestational exposure to ethanol causes fetal alcohol syndrome, which is associated with cerebellar hypoplasia. Previous in vitro studies demonstrated ethanol-impaired neuronal survival with reduced signaling through the insulin receptor (IR). We examined insulin signaling in an experimental rat model of chronic gestational exposure to ethanol in which the pups exhibited striking cerebellar hypoplasia with increased apoptosis. Immunoprecipitation and Western blot analyses detected reduced levels of tyrosyl-phosphorylated IR, tyrosyl-phosphorylated insulin receptor substrate-1 (IRS-1), and p85-associated IRS-1 but no alterations in IR, IRS-1, or p85 protein expression in cerebellar tissue from ethanol-exposed pups. In addition, ethanol exposure significantly reduced the levels of total phosphoinositol 3-kinase, Akt kinase, phospho-BAD (inactive), and glyceraldehyde-3-phosphate dehydrogenase and increased the levels of glycogen synthase kinase-3 activity, activated BAD, phosphatase and tensin homolog deleted in chromosome 10 (PTEN) protein, and PTEN phosphatase activity in cerebellar tissue. Cerebellar neurons isolated from ethanol-exposed pups had reduced levels of insulin-stimulated phosphoinositol 3-kinase and Akt kinase activities and reduced insulin inhibition of PTEN and glycogen synthase kinase-3 activity. The results demonstrate that cerebellar hypoplasia produced by chronic gestational exposure to ethanol is associated with impaired survival signaling through insulin-regulated pathways, including failure to suppress PTEN function.

Received for publication, January 14, 2003 , and in revised form, March 30, 2003.

^* Supported by National Institutes of Health COBRE Grant P20RR15578 and Grants AA02666, AA-02169, AA-11431, and AA12908. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Pierre Galletti Research Bldg., Rhode Island Hospital, 55 Claverick St., Rm. 419, Providence, RI 02903. Tel.: 401-444-7364; Fax: 401-444-2939; E-mail: Suzanne_DeLaMonte_MD{at}Brown.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Kang, X. Chen, B. M. Sebastian, B. T. Pratt, I. R. Bederman, J. C. Alexander, S. F. Previs, and L. E. Nagy Chronic Ethanol and Triglyceride Turnover in White Adipose Tissue in Rats: INHIBITION OF THE ANTI-LIPOLYTIC ACTION OF INSULIN AFTER CHRONIC ETHANOL CONTRIBUTES TO INCREASED TRIGLYCERIDE DEGRADATION J. Biol. Chem., September 28, 2007; 282(39): 28465 - 28473. [Abstract] [Full Text] [PDF]

				P. Huang, Y. M. Altshuller, J. C. Hou, J. E. Pessin, and M. A. Frohman Insulin-stimulated Plasma Membrane Fusion of Glut4 Glucose Transporter-containing Vesicles Is Regulated by Phospholipase D1 Mol. Biol. Cell, June 1, 2005; 16(6): 2614 - 2623. [Abstract] [Full Text] [PDF]