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Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death

Mathieu Vinken, Elke Decrock (UGent) , Elke De Vuyst (UGent) , Marijke De Bock (UGent) , Roosmarijn Vandenbroucke (UGent) , Bruno De Geest (UGent) , Jo Demeester (UGent) , Niek Sanders (UGent) , Tamara Vanhaecke, Luc Leybaert (UGent) , et al.
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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.
Keywords
Primary hepatocyte, Gap junction, Apoptosis, Connexin32, Hemichannel, GAP-JUNCTION CHANNELS, RAT HEPATOCYTES, ACTIVATED MICROGLIA, PRIMARY CULTURE, IDENTIFICATION, TRICHOSTATIN, PROPAGATION, SURVIVAL, NECROSIS, RELEASE

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Chicago
Vinken, Mathieu, Elke Decrock, Elke De Vuyst, Marijke De Bock, Roosmarijn Vandenbroucke, Bruno De Geest, Jo Demeester, et al. 2010. “Connexin32 Hemichannels Contribute to the Apoptotic-to-necrotic Transition During Fas-mediated Hepatocyte Cell Death.” Cellular and Molecular Life Sciences 67 (6): 907–918.
APA
Vinken, M., Decrock, E., De Vuyst, E., De Bock, M., Vandenbroucke, R., De Geest, B., Demeester, J., et al. (2010). Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death. CELLULAR AND MOLECULAR LIFE SCIENCES, 67(6), 907–918.
Vancouver
1.
Vinken M, Decrock E, De Vuyst E, De Bock M, Vandenbroucke R, De Geest B, et al. Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death. CELLULAR AND MOLECULAR LIFE SCIENCES. 2010;67(6):907–18.
MLA
Vinken, Mathieu, Elke Decrock, Elke De Vuyst, et al. “Connexin32 Hemichannels Contribute to the Apoptotic-to-necrotic Transition During Fas-mediated Hepatocyte Cell Death.” CELLULAR AND MOLECULAR LIFE SCIENCES 67.6 (2010): 907–918. Print.
@article{805294,
  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.},
  author       = {Vinken, Mathieu and Decrock, Elke and De Vuyst, Elke and De Bock, Marijke and Vandenbroucke, Roosmarijn and De Geest, Bruno and Demeester, Jo and Sanders, Niek and Vanhaecke, Tamara and Leybaert, Luc and Rogiers, Vera},
  issn         = {1420-682X},
  journal      = {CELLULAR AND MOLECULAR LIFE SCIENCES},
  keyword      = {Primary hepatocyte,Gap junction,Apoptosis,Connexin32,Hemichannel,GAP-JUNCTION CHANNELS,RAT HEPATOCYTES,ACTIVATED MICROGLIA,PRIMARY CULTURE,IDENTIFICATION,TRICHOSTATIN,PROPAGATION,SURVIVAL,NECROSIS,RELEASE},
  language     = {eng},
  number       = {6},
  pages        = {907--918},
  title        = {Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death},
  url          = {http://dx.doi.org/10.1007/s00018-009-0220-2},
  volume       = {67},
  year         = {2010},
}

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