Ethanol impairs insulin-stimulated neuronal survival in the developing brain role of pten phosphatase
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Xu J. | - |
dc.contributor.author | Yeon J.E. | - |
dc.contributor.author | Chang H. | - |
dc.contributor.author | Tison G. | - |
dc.contributor.author | Chen G.J. | - |
dc.contributor.author | Wands J. | - |
dc.contributor.author | De la Monte S. | - |
dc.date.available | 2020-11-03T19:46:35Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/21564 | - |
dc.description.abstract | 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 (IRβ). 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 IRβ, tyrosyl-phosphorylated insulin receptor substrate-1 (IRS-1), and p85-associated IRS-1 but no alterations in IRβ, 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. | - |
dc.format.extent | 9 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.title | Ethanol impairs insulin-stimulated neuronal survival in the developing brain role of pten phosphatase | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1074/jbc.M300401200 | - |
dc.identifier.scopusid | 2-s2.0-0038711749 | - |
dc.identifier.bibliographicCitation | Journal of Biological Chemistry, v.278, no.29, pp 26929 - 26937 | - |
dc.citation.title | Journal of Biological Chemistry | - |
dc.citation.volume | 278 | - |
dc.citation.number | 29 | - |
dc.citation.startPage | 26929 | - |
dc.citation.endPage | 26937 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | Brain | - |
dc.subject.keywordPlus | Chromosomes | - |
dc.subject.keywordPlus | Insulin | - |
dc.subject.keywordPlus | Cerebellar hypoplasia | - |
dc.subject.keywordPlus | Ethanol | - |
dc.subject.keywordPlus | alcohol | - |
dc.subject.keywordPlus | glyceraldehyde 3 phosphate dehydrogenase | - |
dc.subject.keywordPlus | glycogen synthase kinase 3 | - |
dc.subject.keywordPlus | insulin | - |
dc.subject.keywordPlus | insulin receptor | - |
dc.subject.keywordPlus | insulin receptor substrate 1 | - |
dc.subject.keywordPlus | phosphatidylinositol 3 kinase | - |
dc.subject.keywordPlus | phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase | - |
dc.subject.keywordPlus | protein BAD | - |
dc.subject.keywordPlus | protein kinase B | - |
dc.subject.keywordPlus | protein p85 | - |
dc.subject.keywordPlus | animal cell | - |
dc.subject.keywordPlus | animal experiment | - |
dc.subject.keywordPlus | animal model | - |
dc.subject.keywordPlus | apoptosis | - |
dc.subject.keywordPlus | article | - |
dc.subject.keywordPlus | brain development | - |
dc.subject.keywordPlus | cell survival | - |
dc.subject.keywordPlus | cerebellum hypoplasia | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | enzyme activity | - |
dc.subject.keywordPlus | immunoprecipitation | - |
dc.subject.keywordPlus | nerve cell stimulation | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | prenatal exposure | - |
dc.subject.keywordPlus | priority journal | - |
dc.subject.keywordPlus | protein expression | - |
dc.subject.keywordPlus | protein phosphorylation | - |
dc.subject.keywordPlus | rat | - |
dc.subject.keywordPlus | signal transduction | - |
dc.subject.keywordPlus | Western blotting | - |
dc.subject.keywordPlus | 1-Phosphatidylinositol 3-Kinase | - |
dc.subject.keywordPlus | Alcoholism | - |
dc.subject.keywordPlus | Animals | - |
dc.subject.keywordPlus | Animals, Newborn | - |
dc.subject.keywordPlus | Cell Survival | - |
dc.subject.keywordPlus | Cerebellum | - |
dc.subject.keywordPlus | Disease Models, Animal | - |
dc.subject.keywordPlus | Ethanol | - |
dc.subject.keywordPlus | Female | - |
dc.subject.keywordPlus | Fetal Alcohol Syndrome | - |
dc.subject.keywordPlus | Humans | - |
dc.subject.keywordPlus | Insulin | - |
dc.subject.keywordPlus | Maternal-Fetal Exchange | - |
dc.subject.keywordPlus | Neurons | - |
dc.subject.keywordPlus | Phosphoproteins | - |
dc.subject.keywordPlus | Phosphoric Monoester Hydrolases | - |
dc.subject.keywordPlus | Pregnancy | - |
dc.subject.keywordPlus | Pregnancy Complications | - |
dc.subject.keywordPlus | PTEN Phosphohydrolase | - |
dc.subject.keywordPlus | Rats | - |
dc.subject.keywordPlus | Receptor, Insulin | - |
dc.subject.keywordPlus | Signal Transduction | - |
dc.subject.keywordPlus | Tumor Suppressor Proteins | - |
dc.subject.keywordPlus | Animalia | - |
dc.subject.keywordAuthor | PTEN | - |
dc.subject.keywordAuthor | neuron | - |
dc.subject.keywordAuthor | survival | - |
dc.subject.keywordAuthor | brain | - |
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