Modulation of phospholipid metabolism in murine keratinocytes by tumor promoter, 12-O-tetradecanoylphorbol-13-acetate
The possibility that phospholipid deacylation may be a critical event in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-associated effects on mouse skin prompted us to examine in vitro the effects of TPA on arachidonic acid metabolism in neonatal mouse keratinocytes. Three-day old neonatal keratinocytes were prelabeled with ( UC)arachidonic acid (( UC)AA) and ( UC) stearic acid (( UC)ST) and used to characterize the lipases that were activated when these cells were treated with TPA in culture. Data from these studies demonstrate that phosphatidylcholine (PC) and phosphatidylinositol (PI) are the major phospholipids that undergo early hydrolysis to release arachidonic acid when challenged by TPA. Of particular interest was the novel observation of the hydrolysis of UC-labeled PI in these keratinocytes, the accumulation of ( UC)1,2-diacylglyceride and the lack of the ( UC)diacylglyceride phosphorylation to form ( UC)phosphatidic acid. This lack of ( UC) phosphatidic accumulation implied that although TPA enhanced the hydrolysis of ( UC)PI resulting in increased ( UC)diacylglyceride it did not enhance the resynthesis of the ( UC)PI via the phosphorylation of the ( UC)diacylglyceride. Therefore, TPA probably is not involved in the turnover of PI in these cells but is involved in the activation of PC hydrolyzing phospholipase A2 and PI hydrolyzing phospholipase C in these keratinocytes releasing arachidonic acid which then undergoes oxygenation reactions to provide biologically active eicosanoids.
- Research Organization:
- Univ. of California, Davis
- OSTI ID:
- 6235627
- Journal Information:
- J. Invest. Dermatol.; (United States), Journal Name: J. Invest. Dermatol.; (United States) Vol. 4; ISSN JIDEA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550301 -- Cytology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ARACHIDONIC ACID
BIOLOGICAL EFFECTS
BODY
CARBOHYDRATES
CARBON 14 COMPOUNDS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CARCINOGENS
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERASES
ESTERS
FIBROBLASTS
HYDROLASES
INOSITOLS
KERATIN
LABELLED COMPOUNDS
LIPASE
LIPIDS
MAMMALS
METABOLISM
MICE
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
NEONATES
OCTADECANOIC ACID
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHORBOL ESTERS
PHOSPHOLIPIDS
PROTEINS
RODENTS
SACCHARIDES
SCLEROPROTEINS
SKIN
SOMATIC CELLS
VERTEBRATES