title: Endogenous prostaglandins E2 and F 2alpha serve as an anti-apoptotic factor against apoptosis induced by tumor necrosis factor-alpha in mouse 3T3-L1 preadipocytes.
abstract: Adipocytes can function as endocrine cells secreting a variety of adipocytokines including tumor necrosis factor (TNF)-alpha. Treatment of cultured mouse 3T3-L1 preadipocytes with TNF-alpha induced apoptosis, as was evident from increases in nuclear condensation and caspase-3 activity, but differentiated adipocytes during the maturation phase showed resistance to apoptosis by TNF-alpha. Antioxidants effectively reduced TNF-alpha-induced apoptosis in preadipocytes, indicating the involvement of reactive oxygen species. Exposure of preadipocytes to calcium ionophore A23187 reduced TNF-alpha-induced apoptosis, which was accompanied by increased production of prostaglandins (PGs) E2 and PGF 2alpha. TNF-alpha preferentially promoted gene expression of cyclooxygenase (COX)-2 without affecting that of COX-1. Consistently, NS-398, a COX-2 inhibitor, stimulated TNF-alpha-induced apoptosis, which was reversed by exogenous PGE2 and PGF 2alpha. These results indicate that endogenous PGE2 and PGF 2alpha synthesized by preadipocytes through the induction of COX-2 can serve as anti-apoptotic factors against apoptosis by TNF-alpha.
authors.affiliation: Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane University, Matsue, Shimane, Japan. knishimu@shimane-u.ac.jp
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishimura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Setoyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tsumagari
authors.forename: Nana
authors.initials: N
authors.lastname: Miyata
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hatano
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Jisaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nagaya
authors.forename: Kazushige
authors.initials: K
authors.lastname: Yokota
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000166:cytology* / Q000201:enzymology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000502:physiology*; D015232:Dinoprostone / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D009578:Nitrobenzenes / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D007476:Ionophores; D009578:Nitrobenzenes; D011453:Prostaglandins; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D000001:Calcimycin; D012313:RNA; D015237:Dinoprost; D051546:Cyclooxygenase 2; D053148:Caspase 3; D015232:Dinoprostone