Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-11-16
pubmed:abstractText
Cerebellar granule cell neurons undergo apoptotic cell death when subjected to serum-free conditions at physiological concentrations of potassium (5 mM). Protein kinase C (PKC) is known to play a role in preventing neuronal apoptosis under trophic factor deprivation, but its role in protecting cerebellar neurons from cell death under conditions of low potassium is unknown. This study sought to determine the involvement of PKC in neuronal survival and to determine if PKC regulated the phosphatidylinositol 3-kinase (PI 3-K)/Akt pathway in low physiologic concentrations of potassium. Incubation with a pan-PKC inhibitor, Ro-31-8220 (2 microm), or a specific PKCAlpha inhibitor, Gö6976, protected cerebellar granule cell neurons from low potassium-mediated cell death. In contrast, phorbol ester (TPA, 100 nm), a PKC activator, increased cell death. Incubation with, Ro-31-8220 rescued neurons from cell death induced by the PI 3-K inhibitor, LY294002, suggesting that Ro-31-8220 may affect Akt phosphorylation. Western blot analysis showed that serum-free, low potassium conditions decreased Akt phosphorylation, which was exacerbated by treatment with LY294002. In contrast, PKC inhibitors, Gö6976 or Ro-31-8220, increased Akt phosphorylation approximately two and four-fold, respectively in low potassium conditions. Because Akt activation appears to be critical in promoting neuronal survival under these culture conditions, increased Akt phosphorylation brought about by inhibiting PKC promotes neuronal survival.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1029-8428
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
281-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Inhibition of protein kinase C promotes neuronal survival in low potassium through an Akt-dependent pathway.
pubmed:affiliation
Department of Neurology and Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
pubmed:publicationType
Journal Article, Comparative Study