title: Cold-induced apoptosis of rat liver endothelial cells: contribution of mitochondrial alterations.
abstract: BACKGROUND
  Maintenance of the integrity of the vascular endothelium is a critical issue in liver preservation, but hypothermia, applied for cellular protection, induces apoptotic cell death in liver endothelial cells. This cold-induced apoptosis is mediated by an iron-dependent formation of reactive oxygen species. Here, we study the involvement of mitochondria in this process.
  
  
  METHODS
  Cultured rat liver endothelial cells were incubated in cold University of Wisconsin solution for 18 hr and subsequently rewarmed in cell culture medium. Mitochondrial morphology and membrane potential were evaluated using laser scanning microscopy.
  
  
  RESULTS
  During cold incubation in University of Wisconsin solution, a marked, progressive mitochondrial shortening and a reduction in mitochondrial membrane potential occurred. Rewarming of the cells led to mitochondrial ultracondensation, complete loss of the mitochondrial membrane potential, and subsequent apoptotic cell death. The inhibitors of mitochondrial permeability transition, trifluoperazine and fructose, or iron chelation with deferoxamine did not affect mitochondrial shortening during cold incubation but inhibited ultracondensation, loss of mitochondrial membrane potential, and loss of viability during rewarming. Moreover, in these protected cells, an almost complete reestablishment of the mitochondrial membrane potential and morphology could be observed; the few mitochondria that were irreversibly damaged were incorporated into autophagosomes during cellular recovery.
  
  
  CONCLUSIONS
  Two apparently independent mitochondrial alterations take place during cold incubation and subsequent rewarming of liver endothelial cells. Cold-induced mitochondrial shortening represents a reversible process, whereas iron-mediated mitochondrial permeability transition and ultracondensation during rewarming are irreversible and constitute an important mediator of cold-induced apoptosis.
authors.affiliation: Institut für Physiologische Chemie, Universitätsklinikum, Essen, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Kerkweg
authors.forename: Monika
authors.initials: M
authors.lastname: Jacob
authors.forename: Herbert
authors.initials: H
authors.lastname: De Groot
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Mannherz
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004727:Endothelium / Q000166:cytology*; D005632:Fructose / Q000494:pharmacology; D007036:Hypothermia, Induced; D007501:Iron; D008099:Liver / Q000166:cytology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008930:Mitochondria, Liver / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014268:Trifluoperazine / Q000494:pharmacology; D014463:Ultrasonography
chemical_list: D014268:Trifluoperazine; D005632:Fructose; D007501:Iron; D003676:Deferoxamine