Temperature variations in cells, tissues and organs may occur in a number of circumstances. well as apoptosis, was strongly reduced by the radical oxygen species (ROS) scavenger, N-acetylcysteine, Iressa indicating a causal relationship between ROS, DNA damage and cell death during mild cold shock and rewarming. These data bring new insights into the potential deleterious effects of mild hypothermia and rewarming used in various research and therapeutical fields. Iressa Introduction While heat shock has been intensively investigated, cold shock has retained relatively less attention. Cooling at various temperatures and subsequent rewarming however happen even for homeothermic animals or cultured cells, tissues and organs in a number of physiological or accidental situations. Hypothermia is largely used during cardiac surgery or treatment of brain damage. Preservation and transportation of organs and cells usually take place at low temperature, and the production of recombinant proteins is improved by lowering temperature [1C4]). The return to normothermia after cooling induces at least some of the phenotypical changes observed upon hyperthermia, suggesting that cells somehow acclimatize to mild temperature and sense a relative, rather Rabbit Polyclonal to 14-3-3 eta than an absolute, hypothermia [5]. Mild cold stress (25-35C) and heat shock induce somehow similar phenotypical modifications. A general decrease of transcription and translation rate has been reported, although the expression of a subset of temperature-sensitive proteins is not modified or even increased [6,7]. Regulations affecting mRNA stability, alternative transcription start site and splicing decisions have also been documented [8,9]. Reduced metabolism [10,11], cell cycle arrest [12], activation of apoptotic program, disassembly of the cytoskeleton and altered composition or Iressa fluidity of lipidic membranes have been reported [4,11,13]. Contrasting to these features common to both temperature shifts, heat shock can also induce autophagy, a process protecting cells from death [14C16]. Hypothermia has been reported to reduce the level of intracellular reactive oxygen species (ROS) while hyperthermia would stimulate their production [17]. Among a significant number of described cold shock proteins (CSP), only CIRBP (cold-inducible RNA binding protein) and RBM3 (RNA binding motif protein 3), two highly homologous proteins, have been thoroughly characterized. Their expression is rapidly and markedly increased during mild hypothermia, and they appear to be key determinants in cold-stress adaptation and to stimulate translation of cold-specific transcripts through various mechanisms [7,11,18]. CIRBP mRNA expression is transcriptionally controlled via cold-responsive elements in its promoter [4]. The study Iressa of the regulation of the cell cycle by CIRBP has given conflicting data. Cells overexpressing CIRBP at 37C have a reduced growth rate and are mainly arrested in G1 phase [19]. Contrasting to these data, overexpression of CIRBP was reported to immortalize mouse embryo fibroblasts while its down-regulation decreased cell proliferation [20]. RMB3 is also associated with proliferation and considered as a proto-oncogene ( [21], and references therein). The HSP are induced upon heat-shock or upon return to normothermia after a cold shock. Some HSP act as proteins chaperone, preventing misagreggation of denatured proteins and assisting correct refolding upon return to normothermia, while others regulate protein turnover. HSP27, HSP60, HSP70 and HSP90 are generally recognized to prevent apoptosis although some pro-death effects have been described. Some HSP also regulate the redox state of the cells [22]. Our laboratory is involved in space research and investigates the effect of weightlessness on cells phenotype during space flights in autonomous capsules or on the ISS (for detailed descriptions of the experiments, see Erasmus Experiment Archive database from ESA at http://eea.spaceflight.esa.int). The usual experimental time schedule implies a delay Iressa of several days between the preparation of the cell cultures on Earth, their transportation to the site of take off (Cape Canaveral, Baikonour…), integration in the space vessel, launch, orbiting and transfer to the ISS. During this period, cells are usually kept at 22-27C, considered to provide a sleeping mode avoiding disturbances due to vibrations and short periods of hypergravity during launch [23]. Thereafter, cultures are transferred to an incubator at 37C for experiment in microgravity. During preparatory experiments, we observed that morphology was affected by rewarming cells at 37C after several days at 25C. These observations suggested the induction.