Phorbol 12-myristate /3-acetate

Experiments were conducted in which purified trichloroethylene (1 mg in acetone) was applied to the shaved backs of female ICR/Ha Swiss mice (Van Duuren et al. 1979). In an initiation-promotion study, a single application of trichloroethylene was followed by repeated application of phorbol myristate acetate (PMA) promoter. In a second study, mice were treated with trichloroethylene three times per week without a promoter. No significant tumor incidences were observed in these studies. Doses used in these studies were well below the maximum tolerated dose, which is often not reached in dermal studies. 

I. F. and Repine, J.E. (1982). Granulocytes mediate acute edematous lung injury in rabbits and isolated rabbit lungs perfused with phorbol myristate acetate. Am. Rev. Resp. Dis. 125, 443-447. 

PLP Proteolipid protein PLT Primed lymphocyte typing PMA Phorbol myristate acetate PMC Peritoneal mast cell PMN Polymorphonuclear neutrophil... 

FIGURE 7.8 Production of reactive oxygen intermediates by activated macrophages. Cells isolated from the livers of control (CTL) or toxicant (TOX)-treated mice were incubated with phorbol myristate acetate for 15 minutes at 37°C, followed by the indicator dye, DCFH-DA. After 15 minutes, the cells were analyzed for green fluorescence by flow cytometry on a Coulter Cytomics FC500 flow cytometer (Beckman Coulter). For each analysis, at least 10,000 events were collected and analyzed using CXP software. 

FIGURE 7.9 (See color insert) Peroxynitrite production by activated macrophages. Cells isolated from control (CTL) and toxicant (TOX)-treated animals were cultured overnight in the presence of IFNa + LPS. Phorbol myristate acetate was then added. Thirty minutes later, the cells were loaded with DHR 123. After 5 minutes incubation, the cells were rinsed and analyzed for fluorescence associated with peroxynitrite production by confocal microscopy. 

Abbreviations lAA, iodoacetamide BFA, brefeldin A PMA, phorbol myristate acetate DNP, dinitrophenol ATPase, adinosine triphosphatase GTPase, guanosin triphosphatase. 

Holm PK, Eker P, Sandvig K, van Deurs B. Phorbol myristate acetate selectively stimulates apical endocytosis via protein kinase C in polarized cells. Exp Cell Res 1995 217(1) 157-168. 

Shurety W, Bright NA, Luzio JP. The effects of cytochalasin D and phorbol myristate acetate on the apical endocytosis of ricin in polarized Caco-2 cells. J Cell Sci 1996 109 2927-2935. 

Phorbol myristate acetate Smoke Phosphatase, acid Lf ... 

Ogihara. Effects of five Kampohozais on the mitogenic activity of li-popolysaccharide, concanavalin A, Phorbol Myristate acetate and phytohemagglutinin in vivo. J Ethnopharmacol 1986 18(2) 193-204. 

Halenda SP, Volpi M, Zavoico GB, et al Effects of thrombin, phorbol myristate acetate, and prostaglandin D2 on 40-41 kDa protein that is ADP ribosylated by pertussis toxin in platelets. FEES Lett 204 341-346, 1986 Hall RC, Gardner ER, Popkin MK, et al Unrecognized physical illness prompting psychiatric admission a prospective study. Am J Psychiatry 138 629-635, 1981 Hallcher LM, Sherman WR The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem 255 10896-10901, 1980... 

D and E appear to stimulate the formation of 0 directly. The ability of A 23187 to elicit formation of O from PMNs 24,59,60,68.70) appears to be due to its action as an ionophore for Ca (see below). Other active stimuli include fluoride, notable because its effect is reversible human leucocyte pyrogen which might have a function in vivo and phorbol myristate acetate The latter has been very useful as a potent stimulus of the burst in various studies of the kinetics and mechanism of activation of the burst. 

However, the effects of Ca are not seen with all stimuli the production of Of in response to phorbol myristate acetate was unaffected in medium lacking Ca, Lanthanum, which can act as a competitive inhibitor of Ca, reduced the effect of Ca in suspensions of PMNs stimulated with FMLP , That Ca acted by entering the cell was suggested because calcium ions did not affect the binding of FMLP. However, verapamil which blocks the channel for Ca in cell membranes, produced dose-dependent inhibition of the formation of Of and of the influx of Ca. This inhibition could be overcome by increasing the concentration of Ca in the medium . The reasons for the requirement of Ca for activation by some stimuli but not by others might be related to the site at which the stimulus in question acts. PMA, for example, might act at a site beyond the point at which Ca is required. 

In another approach subcellular fractionation of human PMNs, stimulated in vitro with phorbol myristate acetate or opsonized zymsan, was performed by rate-zonal centrifugation in sucrose gradients By varying the centrifugal force the NADPH oxidase could be separated from the activities of enzymes in the lysosomal granules but was similar to the distribution of markers for the plasma membrane, aryl phosphatase, alkaline phosphodiesterase I, and acid aryl phosphatase. 

Van Duuren, B.L., Melchionnc, S. Scidmann, I. (1986) Phorbol myristate acetate and catechol... 

Malcolm, A.R., Mills, L.J. McKenna, E.J. (1985) Effects of phorbol myristate acetate, phorbol dibutyrate, ethanol, dimethylsulfoxide, phenol, and seven metabolites on phenol on metabolic cooperation between Chinese hamster V79 lung fibroblasts. Cell biol. Toxicol., 1, 269-283... 

Woo JH, Lim JH, Kim YH, Suh SI, Min DS, Chang JS, Lee YH, Park JW, Kwon TK. 2004. Resveratrol inhibits phorbol myristate acetate-induced matrix metalloprotei-nase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene 23 1845-1853. 

Aqueous garlic extract in combination with mustard oil reduces the chromosomal aberrations caused by sodium arsenate. Furthermore, both onion and garlic oil decrease the phorbol-myristate-acetate-induced tumor promotion. 

Most substances classified as epigenetic carcinogens are promoters that act after initiation. Manifestations of promotion include increased numbers of tumor cells and decreased length of time for tumors to develop (shortened latency period). Promoters do not initiate cancer, are not electrophilic, and do not bind with DNA. The classic example of a promotor is a substance known chemically as decanoyl phorbol acetate or phorbol myristate acetate, a substance extracted from croton oil. 

The production of reactive oxygen species (ROS) is associated with cytotoxicity. In the CNS, microglia are an important source of these species. In neonatal hamster microglia stimulated with phorbol myristate acetate, a PKC activator, isoproterenol reduces the production of superoxide anion and this decrease was blocked by a P-adrenoreceptors antagonist (Colton and Chernyshev, 1996). 

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