Biomaterial Database

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-accelerated phospholipid metabolism by 5,8,11,14-eicosatetraynoic acid. 1980

P W Wertz, and G C Mueller

The tumor-promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA), accelerates choline phospholipid synthesis in bovine lymphocytes by an oxygen-dependent mechanism. This action is prevented by high concentrations of the cyclooxygenase inhibitor, indomethacin (1 to 3 mM), suggesting a possible involvement of lipid oxidation in the response. The acetylenic analog of arachidonic acid, 5,8,11,14-eicosatetraynoic acid (ETYA), at concentrations in the 10 to 50 microM range also prevents the acceleration of the incorporation of [methyl-3H]choline hydrochloride into choline phospholipids, and it appears more selective in its action. This antagonistic effect of ETYA, an agent which inhibits both the cyclooxygenase and lipoxygenase routes of arachidonic acid oxidation, can be precluded by arachidonic acid but not by other unsaturated or saturated fatty acids. If ETYA is added to lymphocyte cultures after 1 hr of TPA treatment, the established rate of [methyl-3H]choline hydrochloride incorporation is unaffected, but further acceleration is blocked. The inhibition by ETYA cannot be counteracted by any of the prostaglandins, Types A, B, D, E, or F alpha, or by the prostacyclin compounds, PGI1 and 6,9-thia-PGI2. The thromboxane pathway also appears not to be involved since 9,11-azoprosta-5,13-dienoic acid (Azo I), a selective inhibitor of thromboxane synthetase, does not affect the TPA response. These results suggest that TPS may activate the lipoxygenase rather than the cyclooxygenase pathway for lipid oxidation and that an arachidonic acid hydroperoxide or a subsequent metabolite plays a key role in the stimulation of choline phospholipid synthesis by the tumor-promoting phorbol ester, TPA.

UI	MeSH Term	Description	Entries
D010704	Phorbols	The parent alcohol of the tumor promoting compounds from CROTON OIL (Croton tiglium).	Tigliane,Tiglianes
D010743	Phospholipids	Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.	Phosphatides,Phospholipid
D011453	Prostaglandins	A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.	Prostaglandin,Prostanoid,Prostanoids
D011464	Epoprostenol	A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).	Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002794	Choline	A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.	Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D005231	Fatty Acids, Unsaturated	FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.	Fatty Acids, Polyunsaturated,Polyunsaturated Fatty Acid,Unsaturated Fatty Acid,Polyunsaturated Fatty Acids,Acid, Polyunsaturated Fatty,Acid, Unsaturated Fatty,Acids, Polyunsaturated Fatty,Acids, Unsaturated Fatty,Fatty Acid, Polyunsaturated,Fatty Acid, Unsaturated,Unsaturated Fatty Acids
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001095	Arachidonic Acids		Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic
D013755	Tetradecanoylphorbol Acetate	A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.	Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer