Connexin 32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death

Mathieu Vinken, Elke Decrock, Elke De Vuyst, Marijke De Bock, Luc Leybaert, Roosmarijn Vandenbroucke, Bruno De Geest, Joseph Demeester, Niek Sanders, Tamara Vanhaecke, Vera Rogiers

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)907-918
Number of pages12
JournalCellular and Molecular Life Sciences
Volume67
Publication statusPublished - 1 Mar 2010

Keywords

  • connexin 32
  • cell death
  • hepatocyte

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