title: Bubbling cell death: A hot air balloon released from the nucleus in the cold.
abstract: Cell death emanating from the nucleus is largely unknown. In our recent study, we determined that when temperature is lowered in the surrounding environment, apoptosis stops and bubbling cell death (BCD) occurs. The study concerns the severity of frostbite. When exposed to severe cold and strong ultraviolet (UV) irradiation, people may suffer serious damages to the skin and internal organs. This ultimately leads to limb amputations, organ failure, and death. BCD is defined as "formation of a single bubble from the nucleus per cell and release of this swelling bubble from the cell surface to extracellular space that causes cell death." When cells are subjected to UV irradiation and/or brief cold shock (4℃ for 5 min) and then incubated at room temperature or 4℃ for time-lapse microscopy, each cell releases an enlarging nuclear gas bubble containing nitric oxide. Certain cells may simultaneously eject hundreds or thousands of exosome-like particles. Unlike apoptosis, no phosphatidylserine flip-over, mitochondrial apoptosis, damage to Golgi complex, and chromosomal DNA fragmentation are shown in BCD. When the temperature is increased back at 37℃, bubble formation stops and apoptosis restarts. Mechanistically, proapoptotic WW domain-containing oxidoreductase and p53 block the protective TNF receptor adaptor factor 2 that allows nitric oxide synthase 2 to synthesize nitric oxide and bubble formation. In this mini-review, updated knowledge in cell death and the proposed molecular mechanism for BCD are provided.
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC Department of Neuroscience and Physiology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA Department of Neurochemistry, NYS Institute of Basic Research for Developmental Disabilities, Staten Island, NY 10314, USA changns@mail.ncku.edu.tw.
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Chang
mesh_terms: D000818:Animals; D016923:Cell Death; D002467:Cell Nucleus / Q000528:radiation effects*; D003080:Cold Temperature; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D010944:Plants; D014466:Ultraviolet Rays
chemical_list: D009569:Nitric Oxide
keywords: Bubbling cell death; NOS2; UV irradiation; WWOX; apoptosis; cold shock