Linked Life Data

8848016

Source:http://linkedlifedata.com/resource/pubmed/id/8848016

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1996-10-22
pubmed:abstractText
Protein kinase C (PKC), the major receptor for tumor-promoting phorbol esters, is a family consisting of at least 12 distinct isoforms. In C6 glioma cells, short term (10 min) treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) results in a dose-dependent translocation of PKC alpha, PKC delta and PKC theta. Long term (24 hr) treatment with appropriate doses of TPA results in the complete down-regulation of PKC delta but not of PKC alpha PKC theta. This property was used to determine which isoform might be involved in the activation of the glial cell Na(+)-H+ exchanger. It was found that (a) TPA has dose-dependent effects on PKC alpha, PKC delta, and PKC theta translocation and on Na(+)-dependent, EIPA-sensitive Na(+)-H+ exchanger stimulation; (b) the antiporter is blocked both by staurosporine and in cells in which PKC alpha, PKC delta, and PKC theta have been completely down-regulated; (c) the inactive form (alpha-TPA) of TPA, which does not include translocation of the three isoforms (alpha, delta, and theta) has no effect on the antiporter; (d) Western blot analysis demonstrated dose-dependent TPA (10, 30, 100, and 1000 nM)-induced translocation of PKC alpha, PKC delta, and PKC theta. TPA (10, 30, 100, and 1000 nM)-induced Na(+)-H+ exchanger activation was also found to be dose dependent. There was no difference in TPA-induced Na(+)-H+ exchanger activation between 30 and 100 nM; it correlated with the extent of TPA-induced PKC delta translocation over the same concentration range, suggesting that isoform responsible for the exchanger activation is PKC delta; (e) When 1 microM TPA is added after prior treatment of the cells with 10 nM TPA, an additive effect on Na(+)-H+ exchanger is seen that is not observed when the initial stimulus in 30 nM TPA, as would be expected if the PKC delta isoform were responsible for exchanger activation; (f) Finally, when PKC delta, but not PKC alpha and PKC theta, is completely down-regulated by 24-hr pretreatment with 10, 30, or 100 nM TPA, the Na(+)-H+ exchanger can no longer be stimulated by 1 microM TPA; when 1 nM TPA pretreatment is used, no down-regulation occurs and the exchanger still responds to 1 microM TPA. We have shown that the Na(+)-H+ exchanger in C6 glioma cells can be stimulated by TPA-induced PKC activation and, for the first time, that PKC delta is involved in the activation of this antiporter. Our results also suggest that different members of the PKC family within a single cell elicit specific physiological responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
995-1003
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Protein kinase C isoform delta is involved in the stimulation of the Na(+)-H+ exchanger in C6 glioma cells.
pubmed:affiliation
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't