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Biomedical subjects

L Levine

Publications and source records attributed to L Levine.

At least 91 records · Page 5Linked to original sources
PubMed1988

Platelet-activating factor stimulates arachidonic acid metabolism in rat liver cells (C-9 cell line) by a receptor-mediated mechanism.

Platelet activating factor (PAF) stimulated production of prostaglandin (PG) I2, PGE2, and PGF2 alpha by rat liver cells (the C-9 cell line); as little as 0.2 nM PAF was effective. Enantio-PAF was 1000-fold less effective. Lyso-PAF, at levels ranging from 0.1 to 1.0 microM, did not stimulate PGI2 production. The synthesis of PGI2 was essentially complete in 10 min. The stimulation by PAF of PGI2 production was inhibited by the PAF antagonists L-659,989, kadsurenone, L-652,731, and BN 52021; the values for 50% inhibition (IC50) were 0.02, 0.19, 0.21, and 0.73 microM, respectively. The antagonists L-659,989 and BN 52021 had no effect on the levels of 6-keto-PGF1 alpha stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), palytoxin, melittin, the Ca2+ ionophore-A-23187, colchicine, transforming growth factor alpha, or exogenous arachidonic acid. The effect of PAF on arachidonic acid metabolism was inhibited by prior exposure of the cells to PAF. Prior treatment of the rat liver cells at 37 degrees with the TPA-type tumor promoters TPA, teleocidin, and aplysiatoxin, as well as with the second stage tumor promoter mezerein, all of which activate the Ca2+/phospholipid-dependent protein kinase (protein kinase C), resulted not only in homologous desensitization to the TPA-type tumor promoters and mezerein, but also in heterologous desensitization to PAF. Stimulation of PGI2 production by palytoxin, the Ca2+ ionophore A-23187, or exogenous arachidonic acid was not inhibited by such prior treatments with the TPA-type tumor promoters. Prior treatment of the cells at 37 degrees for 30 min with the non-TPA-type tumor promoters okadaic acid or palytoxin, both of which do not activate protein kinase C, did not result in heterologous desensitization to PAF.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Production of antibodies to palytoxin: neutralization of several biological properties of palytoxin.

Palytoxin stimulated arachidonic acid metabolism (in bovine aorta endothelial and smooth muscle cells, rat keratinocytes, porcine aorta endothelial cells and rat liver cells), hemolyzed rat erythrocytes and was lethal to mice when administered intraperitoneally. Serum from rabbits immunized with a conjugate in which palytoxin was covalently bound to bovine albumin through its free amino group neutralized these biologic activities of palytoxin. Ninety-nine per cent of the neutralizing activity of the immunized rabbit serum was removed after precipitation of the rabbit IgG with a goat anti-rabbit IgG.

Acrylamides↗
PubMed1987

Increased arachidonic acid metabolites from cells in culture after treatment with the phosphatidylcholine-hydrolyzing phospholipase C from Bacillus cereus.

Treatment of rat liver cells (the C-9 cell line), porcine aorta endothelial cells, bovine aorta smooth muscle cells, bovine aorta endothelial cells, mouse fibroblasts and rat keratinocytes with highly purified, crystallized Bacillus cereus phospholipase C, which hydrolyzes phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine but has little or no effect on phosphatidylinositol, phosphatidylglycerol, cardiolipin, sphingomyelin, lysophosphatidylcholine or lysophosphatidylethanolamine, increased metabolism of arachidonic acid. Hydrolysis of phosphatidylcholine (and/or phosphatidylethanolamine) by a phosphatidylcholine (or phosphatidylethanolamine)-hydrolyzing phospholipase C appears to contribute to liberation of substrate for arachidonic acid metabolism.

Animals↗
PubMed1987

Modulation of arachidonic acid metabolism in a cultured newborn rat keratinocyte cell line.

Newborn rat keratinocytes, the NBR cell line, synthesized the cyclooxygenase metabolic products, prostaglandins E2 and F2 alpha, and the lipoxygenase metabolic product, hydroxyeicosatetraenoic acid. This metabolism was stimulated by incubation of the cells with the Ca++ ionophore, A23187; melittin; bradykinin; recombinant human f-met epidermal growth factor; the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate; and the synthetic analog of diacylglycerol, 1-oleoyl-2-acetyl glycerol. Production of the cyclooxygenase products was inhibited by the synthetic glucocorticoid, dexamethasone. The stimulation appeared to be modulated by deesterification of arachidonic acid from the cellular lipids, presumably by phospholipase A2. Increased intracellular levels of Ca++ and phosphorylating activities that result from polyphosphoinositol turnover as well as phosphorylating activities independent of phosphatidylinositol turnover appear to be regulating phospholipase A2 hydrolysis of phospholipids.

Animals↗
PubMed1987

Palytoxin: an extraordinarily potent stimulator of prostaglandin production and bone resorption in cultured mouse calvariae.

Palytoxin, a nonphorbol ester-type tumor promoter, stimulated the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvariae in organ culture. The action of palytoxin on bone resorption occurred at extraordinarily low concentrations; enhanced resorption was regularly observed at 0.5 pg/ml, and the ED50 was 1-2 pg/ml (approximately 3 X 10(-13) M). Palytoxin-induced formation of PGE2 and bone resorption were inhibited completely by indomethacin (200 ng/ml). Concentrations of palytoxin above 10 pg/ml led to progressively decreasing enhancement of bone resorption; by 100-250 pg/ml no stimulation of resorption was observed despite continued high production of PGE2. Treatment with high concentrations of palytoxin (100 or 250 pg/ml) for 24-72 h inhibited cAMP accumulation stimulated by exogenous PGE2 or PTH and inhibited bone resorption induced by PGE2, PTH, or an analog of cAMP. Thus, palytoxin exhibited a biphasic dose-response curve for enhanced bone resorption, with stimulation at low concentrations (0.5-10 pg/ml) and toxic inhibition at high concentrations (greater than 50 pg/ml). Palytoxin is one of the most potent stimulators of bone resorption yet identified.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Tumor necrosis factor-alpha (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism.

Recombinant human (h) and murine (m) tumor necrosis factor (TNF)-alpha stimulated bone resorption and the production of prostaglandin (PG) E2 in neonatal mouse calvaria in organ culture. In experiments of 72-h duration, the effect on bone resorption was of large magnitude (an average increase in medium calcium of 3.3 mg/dl above control values in 11 separate experiments) and occurred over a concentration range of 0.1-20 ng/ml mTNF and 0.5-50 ng/ml hTNF. Accompanying the TNF-enhanced release of bone calcium there was enhanced accumulation of PGE2 in the culture medium. The increases in medium calcium and PGE2 were both inhibited completely by nontoxic concentrations of 4 different PG cyclooxygenase inhibitors (indomethacin, piroxicam, ibuprofen, and acetylsalicylic acid) but not by the noncyclooxygenase inhibitor salicylic acid. The magnitude of the PGE2 response, but not the calcium release, was less for bones treated with TNF than for those treated with equipotent doses of epidermal growth factor or human transforming growth factors-alpha or -beta, suggesting that the local site of production of PGE2 in bone may be different for TNF than for the other factors. Repeated sc injections of hTNF to intact mice for a 48-h period produced a statistically significant elevation of the plasma calcium concentration. Because TNF is produced by cells of the monocyte/macrophage lineage in response to invasive stimuli such as the presence of tumor, our findings indicate that a host factor produced in response to malignant cells can cause enhanced bone resorption. Thus, the concept of the humoral hypercalcemias of malignancy must be expanded to include mediators not produced by the tumor cells themselves.

Animals↗
PubMed1986

A protein from the marine mollusc Aplysia californica that is hemolytic and stimulates arachidonic acid metabolism in cultured mammalian cells.

Aqueous extracts of the foot muscle of the marine mollusc Aplysia californica contain a proteins(s) that stimulates cytolysis and prostaglandin production in the C-9 rat liver cell line and hemolysis of red blood cells. Partial purification of the protein by ion exchange chromatography and fast protein liquid chromatography resulted in parallel increases in specific activity for prostaglandin production and hemolysis. Prostaglandin release occurred both at cytolytic concentrations of the protein and at lower concentrations that caused no apparent alterations in cell morphology. Differential sensitivity of a variety of cell lines to stimulation of prostaglandin production was observed; one group of cells, including the C-9 rat liver cell line, displayed a 5-fold stimulation of arachidonic acid metabolism with 1-3 micrograms of a partially purified protein preparation, while a second group was insensitive to concentrations as high as 20 micrograms protein of that preparation. Red blood cells also displayed differential sensitivity to hemolysis: rhesus and squirrel monkey red blood cells were 100-fold more sensitive to lysis by the protein than cebus monkey erythrocytes. Both activities were abolished by treatment with pepsin, trypsin or heat and both had a molecular weight of congruent to 45,000, as determined by gel filtration. Stimulation of both prostaglandin synthesis and hemolysis was Ca2+ dependent. These observations suggest, but do not prove, that the protein that causes lysis of red blood cells and the protein that stimulates arachidonic acid metabolism in the C-9 cell line is the same.

Animals↗
PubMed1986

Combinations of palytoxin or 12-O-tetradecanoylphorbol-13-acetate and recombinant human insulin growth factor-I or insulin synergistically stimulate prostaglandin production in cultured rat liver cells and squirrel monkey aorta smooth muscle cells.

In the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) or the non-TPA-type tumor promoter, palytoxin, recombinant human insulin growth factor-I (IGF-I) and insulin synergistically stimulate prostaglandin production in rat liver cells (the C-9 cell line). Combinations of palytoxin or TPA with recombinant human IGF-I or insulin also synergistically stimulate deesterification of cellular lipids in C-9 cells prelabelled with [3H]arachidonic acid. With both types of stimulations, prostaglandin production or deesterification, the synergistic response of the IGF-I and insulin is greater with palytoxin than with TPA. Production of prostaglandin E2 and F2 alpha by squirrel monkey smooth muscle cells incubated in the presence of TPA and insulin also is greater than the sum of the two effects taken independently.

Acrylamides↗
PubMed1986

Stimulation of arachidonic acid metabolism: differences in potencies of recombinant human interleukin-1 alpha and interleukin-1 beta on two cell types.

Recombinant human interleukin-l (rIL-1) alpha and beta, which have 26% homology in their amino acid sequence, stimulated arachidonic acid metabolism by squirrel monkey smooth muscle cells and rat liver cells; their relative effectiveness, however, varied with the two cells. Recombinant IL-1 alpha was 3 times more effective than rIL-1 beta at stimulating arachidonic acid metabolism by the primate smooth muscle cells. Recombinant IL-1 alpha was 3 times less effective than rIL-1 beta when measured by their capacity to synergistically stimulate arachidonic acid metabolism of rat liver cells in the presence of palytoxin and anti-diuretic hormone (ADH). The rIL-1 alpha and rIL-1 beta also stimulated the release of radiolabelled arachidonic acid from the smooth muscle cells prelabelled with [3H]arachidonic acid. The two recombinant IL-1s have different heat stabilities, again when measured by their capacity to stimulate arachidonic acid metabolism; IL-1 alpha was more heat stable than IL-1 beta.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

A combination of palytoxin with 1-oleoyl-2-acetyl-glycerol (OAG) or insulin or interleukin-1 synergistically stimulates arachidonic acid metabolism, but combinations of 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters with OAG do not.

The combination of palytoxin and 1-oleoyl-2-acetyl-glycerol (OAG) synergistically stimulates production of 6-keto-PGF1 alpha and PGF2 alpha by rat liver cells (the C-9 cell line). In contrast, the combination of 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters (TPA, dihydroteleocidin B, aplysiatoxin, phorbol-12,13-didecanoate) and OAG does not. Production of 6-keto-PGF1 alpha by palytoxin added with recombinant murine interleukin-1 (IL-1) or with insulin is also greater than the sum of the two effects taken independently. Palytoxin and OAG individually stimulate the release of radiolabeled compounds from the rat liver cells pre-labeled with [3H]arachidonic acid and also act synergistically to release labeled metabolites. After separation by h.p.l.c., these materials co-chromatograph with authentic 6-keto-PGF1 alpha and arachidonic acid. The synergistic stimulation by palytoxin and OAG is biphasic; a rapid synergistic production of 6-keto-PGF1 alpha or release of radiolabel from [3H]arachidonic acid prelabeled cells is followed, after approximately 2-4 h, by a prolonged synergistic response.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Actions of growth factors on plasma calcium. Epidermal growth factor and human transforming growth factor-alpha cause elevation of plasma calcium in mice.

Specific humoral substances produced and secreted by human tumors that cause hypercalcemia have not been identified. Certain growth factors (such as epidermal growth factor, platelet-derived growth factor, and transforming growth factors-alpha and -beta) have been shown to stimulate the resorption of bone in organ culture by both prostaglandin-dependent and prostaglandin-independent pathways. In this report we demonstrate that epidermal growth factor and recombinant human transforming growth factor-alpha induce a significant rise in plasma calcium concentration when administered repeatedly to intact mice for periods ranging from 24 h to 16 d. The elevation of plasma calcium is not dependent on dietary calcium and is not invariably accompanied by an increase in systemic levels of the prostaglandin E2 metabolite 13,14-dihydro-15-keto-prostaglandin E2. The in vivo calcium-mobilizing activity of epidermal growth factor and transforming growth factor-alpha indicate that these or related growth factors need be considered as potential mediators of tumor-induced hypercalcemia.

Animals↗
PubMed1986

Effects of atropine on thermoregulatory responses to exercise in different environments.

The thermoregulatory effects of atropine (2 mg im) were examined in six heat-acclimated subjects during exercise in three environments, which provided different evaporative capacities, but similar heat stress as indicated by the wet bulb, globe temperature index (WBGT). Subjects walked in environments of Ta = 42.3 degrees C, Tdp = 14.6 degrees C, WBGT = 29.1 degrees C (HD); Ta = 33.9 degrees C, Tdp = 23.5 degrees C, WBGT = 28.9 degrees C (WM); Ta = 30.4 degrees C, Tdp = 23.8 degrees C, WBGT = 27.4 degrees C, (WW) after atropine and saline injections. In comparison to saline, atropine elevated rectal temperature (Tre) (p less than 0.05) in HD. Additionally, atropine elevated (p less than 0.01) mean skin temperature (Tsk), and heart rate (HR) in all three environments relative to saline. Whole body sweating rate (msw) was 45% lower (p less than 0.01) in each environment after atropine relative to saline. Exercise time was reduced from saline values (p less than 0.05) by 26.5 min in the HD after atropine. Within the atropine treatments, Tre was higher (p less than 0.05) in HD (0.6 degrees C) than WW, and HR was higher (p less than 0.05) in HD (23 b X min-1) and WM (14 b X min-1) than WW. Tsk was higher (p less than 0.01) in WM than WW (1.2 degrees C) and in HD than WM (1.5 degrees C). Exercise time was 26.5 min longer (p less than 0.05) in WW than HD in the atropine experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗