title: Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death.
abstract: The present study was set up to investigate the fate of connexin32 and its channels in hepatocellular apoptosis. Primary hepatocyte cultures were exposed to Fas ligand and cycloheximide, and modifications in connexin32 expression and localization, and gap junction functionality were studied. We found that gap junction functionality rapidly declined upon progression of cell death, which was associated with a decay of the gap junctional connexin32 protein pool. Simultaneously, levels of newly synthesized connexin32 protein increased and gathered in a hemichannel configuration. This became particularly evident towards the end stages of the cell death process and was not reflected at the transcriptional level. We next either silenced connexin32 expression or inhibited connexin32 hemichannel activity prior to cell death induction. Both approaches resulted in a delayed termination of the cell death response. We conclude that connexin32 hemichannels facilitate the apoptotic-to-necrotic transition, which typically occurs in the final stage of hepatocellular apoptosis.
authors: Department of Toxicology, Vrije Universiteit Brussel, Belgium. mvinken@vub.ac.be
authors: Mathieu
authors: M
authors: Vinken
authors: Elke
authors: E
authors: Decrock
authors: Elke
authors: E
authors: De Vuyst
authors: Marijke
authors: M
authors: De Bock
authors: Roosmarijn E
authors: RE
authors: Vandenbroucke
authors: Bruno G
authors: BG
authors: De Geest
authors: Joseph
authors: J
authors: Demeester
authors: Niek N
authors: NN
authors: Sanders
authors: Tamara
authors: T
authors: Vanhaecke
authors: Luc
authors: L
authors: Leybaert
authors: Vera
authors: V
authors: Rogiers
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017630:Connexins / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D008297:Male; D009336:Necrosis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D003513:Cycloheximide; D053222:Fas Ligand Protein; D000097002:Gap Junction beta-1 Protein