Tumor promoting phorbol diesters: substrates for diacylglycerol lipase
Enzyme activity in rat serum was examined utilizing the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and various glycerolipids as substrates. The serum activity was specific for hydrolysis of the long chain tetradecanoate moiety of TPA, hydrolyzed mono- and diacylglycerols, but was not effective against triacylglycerols, cholesterylesters, or phospholipids. Heating the enzyme preparation at 56/sup 0/C for 1 min was dually effective in reducing the hydrolysis of both TPA and dioleoylglycerol by 83-86% of control levels. The potent diacylglycerol lipase inhibitor, RHC 80267, inhibited the hydrolysis of TPA in the 0.2-1.0 ..mu..M range and was also a potent blocker of monoacyl- and diacylglycerol hydrolysis. In substrate competition studies, exogenous unlabeled TPA was added to the (/sup 14/C)dioleoylglycerol-containing reaction mixture, however, this produced an approximate 3-fold stimulation of (/sup 14/)dioleoylglycerol hydrolysis. Although we have not established whether the hydrolysis of TPA and diacylglycerol is the work of one enzyme, the effectiveness of the specific lipase inhibitor, RHC 80267, demonstrates that diacylglycerol lipase can utilize TPA as substrate, a finding never before documented. This point is of interest in light of the theory that phorbol esters act by mimicry of the natural lipid mediator, diacylglycerols. 44 references, 3 figures, 1 table.
- Research Organization:
- Oak Ridge Associated Universities, TN
- OSTI ID:
- 5871776
- Journal Information:
- Biochem. Biophys. Res. Commun.; (United States), Vol. 123:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
LIPASE
ENZYME ACTIVITY
PHORBOL ESTERS
METABOLISM
BIOCHEMISTRY
CARBON 14 COMPOUNDS
ENZYME INHIBITORS
GLYCEROL
HYDROLYSIS
LIPIDS
RATS
SUBSTRATES
TEMPERATURE EFFECTS
TRACER TECHNIQUES
TUMOR PROMOTERS
ALCOHOLS
ANIMALS
CARBOXYLESTERASES
CARCINOGENS
CHEMICAL REACTIONS
CHEMISTRY
DECOMPOSITION
ENZYMES
ESTERASES
ESTERS
HYDROLASES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYSIS
MAMMALS
ORGANIC COMPOUNDS
PROMOTERS
RODENTS
SOLVOLYSIS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)