Source:http://linkedlifedata.com/resource/pubmed/id/16574993
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rdf:type | |
lifeskim:mentions |
umls-concept:C0021469,
umls-concept:C0022023,
umls-concept:C0036536,
umls-concept:C0036537,
umls-concept:C0079411,
umls-concept:C0205191,
umls-concept:C0282639,
umls-concept:C0521116,
umls-concept:C0596119,
umls-concept:C1292733,
umls-concept:C1427539,
umls-concept:C1553655,
umls-concept:C1706144,
umls-concept:C1879547
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pubmed:issue |
2
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pubmed:dateCreated |
2006-7-7
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pubmed:abstractText |
We investigated the effects of PKC-stimulating 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPA) and phorbol 12-myristate 13-acetate (PMA) phorbol esters on cAMP-dependent, forskolin (FSK)-stimulated, short-circuit Cl- current (ISC-cAMP) generation by colonocyte monolayers. These agonists elicited different actions depending on their dose and incubation time; PMA effects at the onset (<5 min) were independent of cAMP agonist and were characterized by transient anion-dependent transcellular and apical membrane ISC generation. DOPPA failed to elicit similar responses. Whereas chronic (24 h) exposure to both agents inhibited FSK-stimulated transcellular and apical membrane ISC-cAMP, the effects of DOPPA were more complex: this conventional PKC-beta-specific agonist also stimulated Ba2+-sensitive basolateral membrane-dependent facilitation of transcellular ISC-cAMP. PMA did not elicit a similar phenomenon. Prolonged exposure to high-dose PMA but not DOPPA led to apical membrane ISC-cAMP recovery. Changes in PKC alpha-, beta1-, gamma-, and epsilon-isoform membrane partitioning and expression correlated with these findings. PMA-induced transcellular ISC correlated with PKC-alpha membrane association, whereas low doses of both agents inhibited transcellular and apical membrane ISC-cAMP, increased PKC-beta1, decreased PKC-beta2 membrane association, and caused reciprocal changes in isoform mass. During the apical membrane ISC-cAMP recovery after prolonged high-dose PMA exposure, an almost-complete depletion of cellular PKC-beta1 and a significant reduction in PKC-epsilon mass occurred. Thus activated PKC-beta1 and/or PKC-epsilon prevented, whereas activated PKC-alpha facilitated, apical membrane ISC-cAMP. PKC-beta-dependent augmentation of transcellular ISC-cAMP at the level of the basolateral membrane demonstrated that transport events with geographically distinct subcellular membranes can be independently regulated by the PKC beta-isoform.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0193-1857
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
291
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G318-30
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16574993-Colon,
pubmed-meshheading:16574993-Cyclic AMP,
pubmed-meshheading:16574993-Enzyme Activation,
pubmed-meshheading:16574993-HT29 Cells,
pubmed-meshheading:16574993-Humans,
pubmed-meshheading:16574993-Ion Channel Gating,
pubmed-meshheading:16574993-Membrane Potentials,
pubmed-meshheading:16574993-Protein Kinase C
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pubmed:year |
2006
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pubmed:articleTitle |
Chronic PKC-beta activation in HT-29 Cl.19a colonocytes prevents cAMP-mediated ion secretion by inhibiting apical membrane current generation.
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pubmed:affiliation |
Department of Integrative Biology, University of Texas Health Science Center, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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