title: UV irradiation/cold shock-mediated apoptosis is switched to bubbling cell death at low temperatures.
abstract: When COS7 fibroblasts and other cells were exposed to UVC irradiation and cold shock at 4°C for 5 min, rapid upregulation and nuclear accumulation of NOS2, p53, WWOX, and TRAF2 occurred in 10-30 min. By time-lapse microscopy, an enlarging gas bubble containing nitric oxide (NO) was formed in the nucleus in each cell that finally popped out to cause "bubbling death". Bubbling occurred effectively at 4 and 22°C, whereas DNA fragmentation was markedly blocked at 4°C. When temperature was increased to 37°C, bubbling was retarded and DNA fragmentation occurred in 1 hr, suggesting that bubbling death is switched to apoptosis with increasing temperatures. Bubbling occurred prior to nuclear uptake of propidium iodide and DAPI stains. Arginine analog Nω-LAME inhibited NO synthase NOS2 and significantly suppressed the bubbling death. Unlike apoptosis, there were no caspase activation and flip-over of membrane phosphatidylserine (PS) during bubbling death. Bubbling death was significantly retarded in Wwox knockout MEF cells, as well as in cells overexpressing TRAF2 and dominant-negative p53. Together, UV/cold shock induces bubbling death at 4°C and the event is switched to apoptosis at 37°C. Presumably, proapoptotic WWOX and p53 block the protective TRAF2 to execute the bubbling death.
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.
authors.forename: Szu-Jung
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Lin
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.
authors.forename: Hsin-Ping
authors.initials: HP
authors.lastname: Lin
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.
authors.forename: Shenq-Shyang
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Chi-Mei Medical Center, Tainan, Taiwan, ROC.
authors.forename: Feng-Jie
authors.initials: FJ
authors.lastname: Lai
authors.affiliation: Department of Dermatology, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.
authors.forename: Hamm-Ming
authors.initials: HM
authors.lastname: Sheu
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.|Center of Infectious Disease and Signaling Research, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors.forename: Li-Jin
authors.initials: LJ
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.|Center of Infectious Disease and Signaling Research, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.|Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan, ROC.|Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.|Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D019556:COS Cells; D016923:Cell Death / Q000502:physiology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003080:Cold Temperature; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D045325:HCT116 Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D009569:Nitric Oxide
keywords: TRAF2; UV; WWOX; cold shock; p53