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Protein kinase C stimulation of phospholipid synthesis in a type II pneumocyte derived cell line

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5325627
;

In the Type II pneumocyte-derived cell line, A549, addition of 50 nM 12-O-tetradecanoyl phorbol-13-acetate (TPA) and phorbol-12, 13-dibutyrate more than doubled the rate of de novo synthesis of phophatidylcholine (PC). A similar increase was observed with the addition of the exogenous diacylglycerol, 1-oleoyl-2-acetylglycerol. These results suggest a role for the activation of protein kinase C(PKC) in the stimulation of PC biosynthesis. The modulation of CTP:phosphocholine cytidyltransferase activity was examined as the locus for TPA mediated effects. Pulse chase experiments showed TPA caused a significant increase in the rate of utilization of phosphocholine. The observed effect of TPA on CT activity may be due to its nonspecific promotion of binding of the enzyme to the endoplasmic reticulum or a specific consequence of PKC activation and phosphorylation. Preincubation of cells with Compound 48/80, an inhibitor of PKC, reduced TPA stimulation of PC synthesis by 40-45%. Incubation with 4..cap alpha..-phorbol 12,13 didecanoate (PDD) which does not activate PKC had little stimulatory effect. Treatment of intact cells with TPA for 60 min increased CT from 0.401 nmol/min/mg to 0.787 nmol/min/mg. Preincubation with 48/80 prior to TPA reduced the increase in CT activity over 50%. Incubation with PDD only increased CT by 17%. These results strongly suggest that the phorbol ester stimulation of phospholipid synthesis is a specific effect due to its ability to activate PKC.

Research Organization:
Univ. of Rochester, NY
OSTI ID:
5325627
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550200 -- Biochemistry
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CARCINOGENS
CELL CONSTITUENTS
CHOLINE
DRUGS
ENDOPLASMIC RETICULUM
ENZYME ACTIVITY
ENZYMES
ESTERS
GLYCEROL
HYDROXY COMPOUNDS
KINETICS
LIPIDS
LIPOTROPIC FACTORS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANOIDS
PHORBOL ESTERS
PHOSPHOLIPIDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
QUATERNARY COMPOUNDS
REACTION KINETICS
SYNTHESIS
TRANSFERASES