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), Journal Name: Biochem. Biophys. Res. Commun.; (United States) Vol. 123:1; ISSN BBRCA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMALS
BIOCHEMISTRY
CARBON 14 COMPOUNDS
CARBOXYLESTERASES
CARCINOGENS
CHEMICAL REACTIONS
CHEMISTRY
DECOMPOSITION
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
ESTERASES
ESTERS
GLYCEROL
HYDROLASES
HYDROLYSIS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPASE
LIPIDS
LYSIS
MAMMALS
METABOLISM
ORGANIC COMPOUNDS
PHORBOL ESTERS
PROMOTERS
RATS
RODENTS
SOLVOLYSIS
SUBSTRATES
TEMPERATURE EFFECTS
TRACER TECHNIQUES
TUMOR PROMOTERS
VERTEBRATES