title: 15-Deoxy-Δ12,14-prostaglandin J2 induces PPARγ- and p53-independent apoptosis in rabbit synovial cells.
abstract: A ligand of peroxisome proliferator-activated receptor γ (PPARγ), 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) induces apoptosis in various cells. However, the mechanism appears to be complex and cell-type specific. We investigated the mechanism of 15d-PGJ2-induced apoptosis of rabbit synovial cells. Exposure to 15d-PGJ2 resulted in DNA fragmentation accompanied by caspase-3 and -9 activations in the cells, suggesting occurrence of mitochondria-mediated apoptosis. Although the exposure also induced remarkable increase in p53 protein, its transcriptional activity was rather reduced, suggesting non-necessity of p53 in 15d-PGJ2-induced apoptosis. Covalent binding of 15d-PGJ2 to cellular proteins including p53 resulted in their insolubilization. N-acetylcysteine inhibited not only the 15d-PGJ2-induced apoptotic events but also the protein insolubilizations via its interaction with 15d-PGJ2. The studies using a PPARγ-agonist and -antagonist showed noninvolvement of PPARγ in 15d-PGJ2-induced apoptosis. The pre-exposure to pro-inflammatory cytokines did not affect the cytotoxicity of 15d-PGJ2 in synovial cells. Taken together, these results show that 15d-PGJ2 induces a mitochondria-mediated apoptotic pathway in p53- and PPARγ-independent manners.
authors.affiliation: Department of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of The Ryukyus, Uehara 207, Nishihara-Cho, Okinawa 903-0215, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sakaba
authors.affiliation: Department of Clinical Physiology, School of Health Sciences, Faculty of Medicine, University of The Ryukyus, Uehara 207, Nishihara-Cho, Okinawa 903-0215, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Awata
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Morisugi
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Department of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of The Ryukyus, Uehara 207, Nishihara-Cho, Okinawa 903-0215, Japan.
authors.forename: Akikazu
authors.initials: A
authors.lastname: Sakudo
authors.affiliation: Department of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of The Ryukyus, Uehara 207, Nishihara-Cho, Okinawa 903-0215, Japan. Electronic address: yatanaka@med.u-ryukyu.ac.jp.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D013582:Synovial Fluid / Q000166:cytology*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D016207:Cytokines; D047495:PPAR gamma; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3; D053179:Caspase 7; D015230:Prostaglandin D2
keywords: 15d-PGJ(2); Apoptosis; Caspase; PPARγ; Synovial; p53