rdf:type |
|
lifeskim:mentions |
umls-concept:C0021853,
umls-concept:C0026046,
umls-concept:C0033634,
umls-concept:C0035820,
umls-concept:C0085403,
umls-concept:C0173022,
umls-concept:C0242275,
umls-concept:C0596235,
umls-concept:C1545588,
umls-concept:C1554080,
umls-concept:C1706198
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pubmed:issue |
5
|
pubmed:dateCreated |
2001-4-9
|
pubmed:abstractText |
Using monolayers of human intestinal (Caco-2) cells, we showed that growth factors (GFs) protect microtubules and barrier integrity against oxidative injury. Studies in nongastrointestinal cell models suggest that protein kinase C (PKC) signaling is key in GF-induced effects and that cytosolic calcium concentration ([Ca2+](i)) is essential in cell integrity. We hypothesized that GF protection involves activating PKC and maintaining normal ([Ca2+](i)) Monolayers were pretreated with epidermal growth factor (EGF) or PKC or Ca2+ modulators before exposure to oxidants (H2O2 or HOCl). Oxidants disrupted microtubules and barrier integrity, and EGF protected from this damage. EGF caused rapid distribution of PKC-alpha, PKC-betaI, and PKC-zeta isoforms to cell membranes, enhancing PKC activity of membrane fractions while reducing PKC activity of cytosolic fractions. EGF enhanced (45)Ca2+ efflux and prevented oxidant-induced (sustained) rises in ([Ca2+](i)). PKC inhibitors abolished and PKC activators mimicked EGF protection. Oxidant damage was mimicked by and potentiated by a Ca2+ ionophore (A-23187), exacerbated by high-Ca2+ media, and prevented by calcium removal or chelation or by Ca2+ channel antagonists. PKC activators mimicked EGF on both (45)Ca2+ efflux and ([Ca2+](i)). Membrane Ca2+-ATPase pump inhibitors prevented protection by EGF or PKC activators. In conclusion, EGF protection of microtubules and the intestinal epithelial barrier requires activation of PKC signal transduction and normalization of ([Ca2+](i)).
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Hypochlorous Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide I,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C beta,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C zeta
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pubmed:status |
MEDLINE
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pubmed:month |
May
|
pubmed:issn |
0193-1857
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
280
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
G828-43
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11292590-Calcimycin,
pubmed-meshheading:11292590-Calcium,
pubmed-meshheading:11292590-Calcium-Transporting ATPases,
pubmed-meshheading:11292590-Cell Membrane,
pubmed-meshheading:11292590-Cell Membrane Permeability,
pubmed-meshheading:11292590-Cytosol,
pubmed-meshheading:11292590-Enzyme Activation,
pubmed-meshheading:11292590-Enzyme Inhibitors,
pubmed-meshheading:11292590-Epidermal Growth Factor,
pubmed-meshheading:11292590-Humans,
pubmed-meshheading:11292590-Hydrogen Peroxide,
pubmed-meshheading:11292590-Hypochlorous Acid,
pubmed-meshheading:11292590-Indoles,
pubmed-meshheading:11292590-Intestinal Mucosa,
pubmed-meshheading:11292590-Isoenzymes,
pubmed-meshheading:11292590-Maleimides,
pubmed-meshheading:11292590-Microtubules,
pubmed-meshheading:11292590-Models, Biological,
pubmed-meshheading:11292590-Oxidants,
pubmed-meshheading:11292590-Protein Kinase C,
pubmed-meshheading:11292590-Protein Kinase C-alpha,
pubmed-meshheading:11292590-Signal Transduction,
pubmed-meshheading:11292590-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11292590-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Key role of PKC and Ca2+ in EGF protection of microtubules and intestinal barrier against oxidants.
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pubmed:affiliation |
Department of Internal Medicine (Division of Digestive Diseases), Rush University Medical Center, 1725 W. Harrison, Suite 206, Chicago, IL 60612, USA. ali_banan@rush.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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