title: 15-Deoxy-Δ(12,14)-prostaglandin J(2) interferes inducible synthesis of prostaglandins E(2) and F(2α) that suppress subsequent adipogenesis program in cultured preadipocytes.
abstract: Cultured preadipocytes enhance the synthesis of prostaglandin (PG) E(2) and PGF(2α) involving the induction of cyclooxygenase (COX)-2 during the growth phase upon stimulation with a mixture of phorbol 12-myristate 13-acetate, a mitogenic factor, and calcium ionophore A23187. Here, we studied the interactive effect of 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) on the inducible synthesis of the endogenous PGs in cultured preadipocytes and its implication in adipogenesis program. 15d-PGJ(2) interfered significantly the endogenous synthesis of those PGs in response to cell stimuli by suppressing the induction of COX-2 following the attenuation of NF-κB activation. In contrast, Δ(12)-PGJ(2) and troglitazone had almost no inhibitory effects, indicating a mechanism independent of the activation of peroxisome proliferator-activated receptor γ for the action of 15-PGJ(2). Pyrrolidinedithiocarbamate (PDTC), an NF-κB inhibitor, effectively inhibited on the inducible synthesis of those PGs in preadipocytes. Endogenous PGs generated by preadipocytes only during the growth phase in response to the cell stimuli autonomously attenuated the subsequent adipogenesis program leading to the differentiation and maturation of adipocytes. These effects were prevented by additional co-incubation of preadipocytes with either 15d-PGJ(2) or PDTC although 15d-PGJ(2) alone has no stimulatory effect. Moreover, 15d-PGJ(2) did not block the inhibitory effects of exogenous PGE(2) and PGF(2α) on the adipogenesis program in preadipocytes. Taken together, 15d-PGJ(2) can interfere the COX pathway leading to the induced synthesis of endogenous PGs that contribute to negative regulation of adipogenesis program in preadipocytes.
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, Nishikawatsu-cho, Matsue, Japan.
authors.forename: Abu Asad
authors.initials: AA
authors.lastname: Chowdhury
authors.forename: Mohammad Sharifur
authors.initials: MS
authors.lastname: Rahman
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishimura
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Jisaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nagaya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shono
authors.forename: Kazushige
authors.initials: K
authors.lastname: Yokota
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D049109:Cell Proliferation; D002839:Chromans / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D015870:Gene Expression; D007476:Ionophores / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000819:agonists; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D000077288:Troglitazone
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002839:Chromans; D007476:Ionophores; D007527:Isoenzymes; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D013859:Thiocarbamates; D014280:Triglycerides; C066229:prolinedithiocarbamate; D016718:Arachidonic Acid; D000001:Calcimycin; D011392:Proline; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D000077288:Troglitazone; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2