Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tannin, a polydisperse polyphenol extracted from cotton bracts (CBE), has been implicated in the pathogenesis of byssinosis, a lung disease of mill workers. CBE tannin inhibits chloride secretion in airway epithelial cells by means of an unknown mechanism(s). Activation of protein kinase C (PKC) by PMA (phorbol 12-myristate 13-acetate) in airway cells increases chloride secretion. The effect of tannin on this PKC pathway was examined, using canine tracheal epithelium mounted in Ussing chambers. PMA addition (10 nM) to the mucosal bath resulted in a 0.36 +/- 0.07 microEq/cm2.h (mean +/- SEM, n = 20) increase in short-circuit current (Isc) and a 0.38 +/- 0.17 microEq/cm2.h increase in net chloride secretion (Jnet). The inactive 4 alpha-phorbol had no effect. Tannin addition to the mucosal bath produced a dose-dependent decrease in Isc and Jnet. In tissues pretreated with 2-50 micrograms/ml tannin, and subsequently stimulated with PMA, tannin inhibited PMA stimulation of chloride secretion beginning at a tannin concentration of 10 micrograms/ml (0.09 +/- 0.05 microEq/cm2.h [n = 10] increase in Isc and 0.08 +/- 0.03 microEq/cm2.h increase in Jnet with PMA after tannin pretreatment). At 50 micrograms/ml tannin, the stimulatory effect of PMA was completely abolished. The known PKC inhibitor, H-7 (20 microM), inhibited PMA stimulation, while chelerythrine (2 microM) had not effect on PMA-stimulated Isc and Jnet, and calphostin C was toxic to the airway epithelium. In membrane fragments, 2.5 micrograms/ml tannin inhibited the rate of histone III phosphorylation by PMA from 32.1 +/- 4.4 nmol/mg protein per min to 20.1 +/- 2.7 nmol/mg protein per min (n = 7). In bovine airway cells, tannin pretreatment (2.5 micrograms/ml) decreased the cytosolic activity of PKC but had no effect on PKC translocation to the membrane. We conclude that tannin inhibits chloride secretion in airway epithelial cells in part by inhibiting PKC.
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PMID:Tannin inhibition of protein kinase C in airway epithelium. 756 89

These experiments were designed to study signal transduction pathways in alveolar macrophages stimulated by condensed tannin or zymosan. Condensed tannins, present in cotton mill dust, alter the host-defense function of alveolar macrophages and may contribute to the pathogenesis of byssinosis. We tried to determine the early steps in signal transduction mechanisms of cell activation by tannin. With the quantification of 51Cr release, we determined that tannin was cytotoxic for the cells after 30 min activation with 130 micrograms for 2 x 10(6) cells. 51Cr release was similar for control cells and zymosan- or 30 micrograms tannin-activated cells. Using the luciferine luciferase reaction, we showed that tannin markedly depleted ATP cell content. In inositol-labeled cells, tannin increased inositolphosphate release in a dose-dependent manner. In lysoPAF-labeled cells, tannin induced synthesis of phosphatidic acid and diglycerides. In the presence of ethanol, the level of tannin-induced phosphatidic acid was slightly reduced, and phosphatidylethanol was synthesized. No phosphatidylethanol was found in alveolar macrophages stimulated by zymosan in the presence of ethanol. GF 109203X, a specific inhibitor of protein kinase C decreased only tannin-induced phosphatidylethanol synthesis. In conclusion, tannin (at 30 or 130 micrograms/ml) activated an inositol phospholipase C in alveolar membranes. Phosphatidylcholine phospholipases C and D were found only at the higher concentration of tannin.
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PMID:Distinct signal transduction pathways for activation of rabbit alveolar macrophages in vitro by cotton bract tannin. 865 14