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Biomedical subjects

R E Moore

Publications and source records attributed to R E Moore.

At least 127 records · Page 7Linked to original sources

Comparative effects of aplysiatoxin, debromoaplysiatoxin, and teleocidin on receptor binding and phospholipid metabolism.

We have compared the activities of aplysiatoxin and debromoaplysiatoxin, two polyacetate marine algae toxins, with teleocidin, a tumor-promoting indole alkaloid from Streptomyces, with respect to inhibition of specific binding of epidermal growth factor, and phorbol-12,13-dibutyrate to their respective receptors and ability to stimulate the release of radioactivity from cells prelabeled with choline or arachidonic acid. Although these compounds have chemical structures that are quite different from the phorbol esters, both aplysiatoxin and teleocidin are essentially equipotent with the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate in all four assays. The fact that aplysiatoxin and teleocidin inhibit phorbol-12,13-dibutyrate-receptor binding suggests that their biological activities are mediated by binding to the same receptors utilized by the phorbol esters. Debromoaplysiatoxin, a debrominated form of aplysiatoxin, is about 10-fold weaker than aplysiatoxin in inhibiting epidermal growth factor and phorbol-12,13-dibutyrate-receptor binding, but is equipotent with aplysiatoxin in stimulating the release of lipid metabolites from the prelabeled cells. The results are discussed in terms of possible heterogeneity of cellular receptors for this group of compounds.

Alkaloids↗

The development and application of a radioimmunoassay for rat phosphoenolpyruvate carboxykinase.

We employed a newly developed radioimmunoassay to quantitate P-enolpyruvate carboxykinase protein directly in liver and kidney of intact rats. The radioimmunoassay was dependent upon the presence of sodium dodecyl sulfate in the competitive binding reaction mixture. In conjunction with assayable activity measurements, the radioimmunoassay results also made it possible to assess the average specific activity of the enzyme. In the fed state, liver P-enolpyruvate carboxykinase was 0.89 microM (micromoles/kg of tissue) and the kidney enzyme was 1.90 microM. Following a 48-h fast, the enzyme in liver increased to 2.83 microM and that in kidney to 6.83 microM. Although liver enzyme concentration increased 3-fold, total liver enzymic activity was increased only about 30%. The discrepancy was due to the decrease in liver weight which occurred during fasting. The kidneys, which do not lose weight during fasting, had a 65% elevation of total organ activity. Total organ enzyme activity was predominantly dependent on changes in enzyme mass. In the fed state, the kidney/liver enzyme mass ratio was 0.44, in the fasted state it was 0.68. Variation in enzyme concentration, enzyme half-life, and response to tryptophan and chronic triamcinolone administration all gave evidence for organ-specific regulation.

Animals↗

The third class of new tumor promoters, polyacetates (debromoaplysiatoxin and aplysiatoxin), can differentiate biological actions relevant to tumor promoters.

Aplysiatoxin is a new class of potent tumor promoter and debromoaplysiatoxin may be a weak promoter. Aplysiatoxin and debromoaplysiatoxin showed the same potency on irritation of mouse ear and induction of ornithine decarboxylase activity on mouse skin, but debromoaplysiatoxin was much weaker than aplysiatoxin in induction of adhesion of HL-60 cells.

Animals↗

Teleocidin, lyngbyatoxin A and their hydrogenated derivatives, possible tumor promoters, induce terminal differentiation in HL-60 cells.

Teleocidin isolated from Streptomyces mediocidicus, its catalytically hydrogenated compound dihydroteleocidin B, and lyngbyatoxin A isolated from marine blue-green alga Lyngbya majuscula as well as its hydrogenated product, tetrahydrolyngbyatoxin A were tested for their ability to induce differentiation of human promyelocytic leukemia cells (HL-60 cells) in culture. All of these indole alkaloids induced differentiation of HL-60 cells, characterized by increased phagocytosis, increased release of lysozyme, and morphological changes resembling macrophages. The concentrations required for the induction were 1-5 ng/ml, showing similarity to those of 12-O-tetradecanoylphorbol-13-acetate (TPA). Teleocidin, lyngbyatoxin A, and tetrahydrolyngbyatoxin A are suggested to be tumor promoters, like TPA and dihydroteleocidin B. The HL-60 cell system might be useful for screening for environmental tumor promoters.

Alkaloids↗

Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters.

Dihydroteleocidin B, which is a derivative of teleocidin from Streptomyces, showed potent tumor-promoting activity in vivo when painted on mouse skin. Although the chemical structure of dihydroteleocidin B is entirely different from those of phorbol esters, the tumor-promoting activity of dihydroteleocidin B was found to be comparable to that of 12-O-tetradecanoylphorbol 13-acetate (TPA) in vivo. Teleocidin from Streptomyces and lyngbyatoxin A and debromoaplysiatoxin from the marine blue-green alga Lyngbya majuscula induced ornithine decarboxylase activity when painted on mouse skin, their effects being similar to those of dihyroteleocidin B and TPA. 13-cis-Retinoic acid inhibited this ornithine decarboxylase induction when painted on the skin 1 hr before these natural products. These three compounds produced adhesion of human promyelocytic leukemia cells (HL-60) to the flasks and inhibited differentiation of Friend erythroleukemia cells induced by dimethyl sulfoxide. The in vitro biological potencies of teleocidin and lyngbyatoxin A were almost as great as those of dihydroteleocidin B and TPA, but that of debromoaplysiatoxin was much weaker.

9,10-Dimethyl-1,2-benzanthracene↗

Endogenous substrate for cyclic AMP-dependent protein kinase in adrenocortical polyadenylated messenger ribonucleoproteins.

An endogenous polysomal cyclic AMP-dependent protein kinase specifically phosphorylates a 150,000-dalton peptide bound to an adrenocortical polyadenylated messenger ribonucleoprotein complex. There is a possibility that this protein is a physiological substrate of cyclic AMP-dependent protein kinase and that the phosphorylation and dephosphorylation of this substrate may be important in the translation control of adrenal polyadenylated messenger RNA.

Adrenal Cortex↗

Antineoplastic evaluation of Pacific basin marine algae.

Extracts of 107 marine alga specimens from Pacific islands were tested for P-388 lymphocytic leukemia and Ehrlich ascites tumor in mice. Several specimens showed high antitumor activity in both systems, with some featuring a notable lack of toxicity.

Animals↗

The differential phosphorylation of free cytoplasmic and membrane-bound polysomal poly(A)mRNP particles in the bovine adrenal cortex.

Free and membrane-bound polysomes were isolated and incubated under in vitro conditions that allowed the phosphorylation of contained poly(A)mRNP complexes. The three phosphoproteins of 150,000, 67,000 and 45,000 daltons were consistently present in the free poly(A)mRNP fraction and absent in the membrane-bound particles. The major phosphoprotein contained in the membrane-bound poly(A)mRNP complexes was 105,000 daltons. This protein was also present in the free cytoplasmic poly(A)mRNP fraction. It is conceivable that protein kinases differentially regulate these two classes of poly(A)mRNP particles through specific phosphorylations of their associated proteins.

Adrenal Cortex↗

Seaweed dermatitis: structure of lyngbyatoxin A.

A highly inflammatory and vesicatory substance, lyngbyatoxin A, has been isolated from the lipid extract of a Hawaiian shallow-water variety of Lyngbya majuscula Gomont; its gross structure was determined from chemical and spectral data. Lyngbyatoxin A is closely related to teleocidin B, a poisonous substance associated with several strains of Streptomyces.

Alkaloids↗