Okadaic acid and dinophysistoxin-1, non-TPA-type tumor promoters, stimulate prostaglandin E2 production in rat peritoneal macrophages

Ohuchi, Kazuo; Tamura, Toshiya; Ohashi, Mariko; Watanabe, Masao; Hirasawa, Noriyasu; Tsurufuji, Susumu; Fujiki, Hirota

doi:10.1016/0167-4889(89)90132-8

Cited by 28 publications

(9 citation statements)

References 17 publications

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“…Stimulation of COX-2 gene expression by thapsigargin and okadaic acid is consistent with previous reports of increased prostaglandin production in response to these agents (12)(13)(14)(15). COX-2 expression has been shown to be increased in rodent skin papillomas and carcinomas promoted by TPA, and rodent skin tumorigenesis can be inhibited by NSAIDS (7).…”

Section: Figsupporting

confidence: 78%

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Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells

Ledwith¹,

Pauley²,

Wagner³

et al. 1997

Journal of Biological Chemistry

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Increased expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin synthesis, has been associated with growth regulation and carcinogenesis in several systems. COX-2 is known to be induced by cytokines and the skin tumor promoter 12-tetradecanoylphorbol-13-myristate (TPA). In the present study, we investigated the effects of several non-TPA-type tumor promoters on COX-2 expression in immortalized mouse liver cells. Specifically, we tested peroxisome proliferators (PPs), which are rodent liver tumor promoters that cause gross alterations in cellular lipid metabolism, the rodent liver tumor promoter phenobarbital, and the skin tumor promoters okadaic acid and thapsigargin. The PPs Wy-14643, mono-ethylhexyl phthalate, clofibrate, ciprofibrate ethyl ester, and eicosatetraynoic acid each caused large increases in COX-2 mRNA and protein, with maximal expression seen approximately 10 h after treatment of quiescent cells. COX-2 expression was also induced by thapsigargin, okadaic acid, and calcium ionophore A23187, but not by phenobarbital or the steroid PP dehydroepiandrosterone sulfate. Induction of COX-2 expression generally resulted in increased synthesis of prostaglandin E 2 (PGE 2 ). However, the PPs caused little or no increase in PGE 2 levels, and they inhibited serum-induced PGE 2 synthesis. Unlike nonsteroidal anti-inflammatory drugs, the PPs do not directly inhibit cyclooxygenase enzyme activity in vitro. Thus, PPs regulate prostaglandin metabolism via both positive (COX-2 induction) and inhibitory mechanisms. In summary, the strong induction of COX-2 expression by PPs, thapsigargin, and okadaic acid suggests a possible role for COX-2 in the growth regulatory activity of these non-TPA-type tumor promoters.

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Section: Figsupporting

confidence: 78%

“…COX-2 expression is increased in skin tumors promoted by TPA, and skin tumorigenesis can be inhibited by NSAIDS (7). Furthermore, both thapsigargin and okadaic acid cause increased prostaglandin synthesis in vitro (12)(13)(14)(15).…”

mentioning

confidence: 99%

Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells

Ledwith¹,

Pauley²,

Wagner³

et al. 1997

Journal of Biological Chemistry

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“…However, okadaic acid required a lag phase, of longer than 4 h, to induce a significant AA release. Whether these results are related to the evidence that okadaic-acid-induced PGE2 production and [ 3 H]AA release from macrophages were inhibited by cycloheximide [20], some proteins could be synthesized during this lag phase in order to express these effects. The mechanism of action by which okadaic acid stimulates AA metabolism by fibroblasts remains to be elucidated.…”

Section: Discussionmentioning

confidence: 72%

“…We find that this effect is consistent with a regulated, growth-dependent change in the activity of PLA 2 , a process regulated by changes in phosphorylation of the enzyme. [5, 6, 8, 9, 11, 12, 14, 15 3H]Arachidonic acid (180-240 Ci/mmol or 6.7 x 10 12 to 8.9 x 10 12 BgImmol), L-a [myo-inositol-2 -3H (N)] phosphatidylinositol (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Ci/mmol or 1.9 x 101! to 7.4 x lo ll Bq/mmol) and L-a-l-palmitoyl-2-arachidonyl [1 -14C] phosphatidylcholine (40-60 mCi/mmol or 1.5 x 10 12 to 2.2x 10 12 Bq/mmol) were obtained from Du Pont-New England Nuclear (Boston, Mass., USA).…”

Section: Introductionmentioning

confidence: 99%

Proliferation-dependent changes in arachidonic acid mobilization from phospholipids of 3T6 fibroblasts

1996

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When we stimulated 3T6 fibroblasts, we observed a mobilization of arachidonic acid (AA) from phospholipids. The magnitude of this response decreased as the cells became confluent and the change coincided with a decrease in the percentage of cells in growth phases (G2 + M); this was not a consequence of the time in culture or a factor in the growth medium. Preconfluent fibroblasts incubated with the calcium ionophore A23187 (1 microM), 4beta-phorbol-12-myristate acetate (PMA, 10 microM), bradykinin (10 microM) or fetal calf serum (20%) released 38.8%, 62.5%, 11.2% and 45.6% [3H]AA, respectively. Confluent cells stimulated under the same conditions released only 16.9%, 1.5%, 0.5% and 18.5% [3H]AA, respectively. This decreasing mobilization of AA was demonstrated using metabolic labelling and measurement of prostaglandin PGE2. The decrease was not due to a changing pool of AA. [3H]AA release from each phospholipid decreased with confluence. Conversion of confluent cells to the proliferative phenotype by mechanical wounding of the monolayer increased the release of [3H]AA. This effect is consistent with regulated, growth-dependent changes in the activity of phospholipase A2, a process regulated by changes in phosphorylation of the enzyme. The increased release of [3H]AA from preconfluent, actively dividing cells may have important physiological implications and may help elucidate mechanisms regulating release of AA.

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“…Although it is not known which specific mechanisms are involved in this inhibition, the results indicate that some protein synthesis is required for this stimulation. The requirement of protein synthesis for the stimulation of AA release by tumor promoters has been shown in a number of studies [33,38]. It is possible that the turnover of phospholipases or a phospholipase regulator is affected by the inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Cellular Mechanisms for Orthovanadate-, Phorbol Ester-, and Calcium Ionophore- Stimulated Prostaglandin Production in Brook Trout (Salvelinus Fontinalis) Follicles1

Hsu

Goetz

1993

Biology of Reproduction

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Previous studies have shown that prostaglandin (PG) production in brook trout (Salvelinus fontinalis) follicles can be stimulated by sodium orthovanadate, phorbol-12 myristate 13-acetate ester (PMA), and the calcium ionophore, A23187. In the present study, the mechanisms by which these activators stimulate PG production in follicles were specifically investigated by examination of their effects on the release of 3H-labeled arachidonic acid (AA) from prelabeled follicles (AA release) and on the capacity to convert exogenous 3H-AA into prostanoids (AA conversion) by follicle walls. The release of AA from follicles was significantly stimulated by orthovanadate and A23187 after 4 h of incubation. Although AA release was not stimulated by PMA alone, levels of AA release in incubations with both PMA and A23187 were greater than in those with A23187 alone. In contrast, AA conversion in follicle walls was significantly increased by PMA and orthovanadate but not by A23187 alone. The results showed that 1) the calcium ionophore A23187 stimulated ovarian PG production mainly through its effects on the release of AA from follicles; 2) PMA enhanced follicular PG production through an increase in AA conversion in the follicle walls; and 3) orthovanadate mediated PG production by increasing both AA release and AA conversion. In addition, PMA-, A23187-, and orthovanadate-stimulated increases in AA release or conversion were significantly reduced by the translational inhibitor, cycloheximide, and the transcriptional inhibitor, actinomycin. These results indicate that PMA-, A23187-, and orthovanadate-stimulated AA release and AA conversion require protein synthesis and pretranslational activation in the follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

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Okadaic acid and dinophysistoxin-1, non-TPA-type tumor promoters, stimulate prostaglandin E2 production in rat peritoneal macrophages

Cited by 28 publications

References 17 publications

Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells

Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells

Proliferation-dependent changes in arachidonic acid mobilization from phospholipids of 3T6 fibroblasts

Cellular Mechanisms for Orthovanadate-, Phorbol Ester-, and Calcium Ionophore- Stimulated Prostaglandin Production in Brook Trout (Salvelinus Fontinalis) Follicles1

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