Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
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)).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G828-43
pubmed:dateRevised
2010-11-18
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
pubmed:year
2001
pubmed:articleTitle
Key role of PKC and Ca2+ in EGF protection of microtubules and intestinal barrier against oxidants.
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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't