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- W2284664188 abstract "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))." @default.
- W2284664188 created "2016-06-24" @default.
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- W2284664188 creator A5088948504 @default.
- W2284664188 date "2001-05-01" @default.
- W2284664188 modified "2023-09-29" @default.
- W2284664188 title "Key role of PKC and Ca<sup>2+</sup>in EGF protection of microtubules and intestinal barrier against oxidants" @default.
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- W2284664188 doi "https://doi.org/10.1152/ajpgi.2001.280.5.g828" @default.
- W2284664188 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11292590" @default.
- W2284664188 hasPublicationYear "2001" @default.
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