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Connexin43 signaling contributes to spontaneous apoptosis in cultures of primary hepatocytes

Mathieu Vinken, Elke Decrock UGent, Tamara Vanhaecke, Luc Leybaert UGent and Vera Rogiers (2012) TOXICOLOGICAL SCIENCES. 125(1). p.175-186
abstract
Primary hepatocyte cultures suffer from the progressive occurrence of dedifferentiation followed by spontaneous apoptosis. This is associated with modifications in the expression of connexins (Cxs), which are the building stones of hemichannels that in turn form gap junctions between neighboring cells. Specifically, a shift is observed from the adult hepatocellular Cx32 species toward the fetal Cx43 isoform. The current study was set up to investigate the role of Cx43 in spontaneous apoptosis taking place in primary hepatocyte cultures. For this purpose, freshly isolated adult rat hepatocytes were cultivated in conventional conditions for 4 days with daily monitoring of Cx expression, Cx localization, and gap junction channel and hemichannel functionality. Gap junction activity was low shortly after isolation, whereas the inverse was observed for hemichannel functionality. Both channel types displayed high activity near the end stages of the cultivation period. The Cx32-to-Cx43 switch became progressively manifested at the translational level. At the transcriptional level, a fivefold decrease in Cx32 messenger RNA abundance and a twofold increase in Cx43 expression were noticed within the first 24 h of cultivation. Throughout the cultivation period, Cx32 was mainly located at the plasma membrane surface, whereas Cx43 immunostaining was more diffuse. Application of three Cx43 inhibitors resulted in the downregulation of both hemichannel functionality and gap junction activity. This was paralleled by decreased expression and activity of caspase 3 as well as by reduced expression of Bid. Collectively, these data show that Cx43 signaling actively contributes to the occurrence of spontaneous apoptosis in cultures of primary hepatocytes.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
primary hepatocyte, apoptosis, connexin43, hemichannel, gap junction, ADULT-RAT HEPATOCYTES, JUNCTIONAL INTERCELLULAR COMMUNICATION, LONG-TERM CULTURE, GAP-JUNCTION, MOLECULAR-MECHANISMS, CELL-PROLIFERATION, OVAL CELLS, EXPRESSION, LIVER, DIFFERENTIATION
journal title
TOXICOLOGICAL SCIENCES
Toxicol. Sci.
volume
125
issue
1
pages
175 - 186
Web of Science type
Article
Web of Science id
000298734400017
JCR category
TOXICOLOGY
JCR impact factor
4.328 (2012)
JCR rank
8/85 (2012)
JCR quartile
1 (2012)
ISSN
1096-6080
DOI
10.1093/toxsci/kfr277
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2106390
handle
http://hdl.handle.net/1854/LU-2106390
date created
2012-05-14 20:50:01
date last changed
2012-05-15 09:30:21
@article{2106390,
  abstract     = {Primary hepatocyte cultures suffer from the progressive occurrence of dedifferentiation followed by spontaneous apoptosis. This is associated with modifications in the expression of connexins (Cxs), which are the building stones of hemichannels that in turn form gap junctions between neighboring cells. Specifically, a shift is observed from the adult hepatocellular Cx32 species toward the fetal Cx43 isoform. The current study was set up to investigate the role of Cx43 in spontaneous apoptosis taking place in primary hepatocyte cultures. For this purpose, freshly isolated adult rat hepatocytes were cultivated in conventional conditions for 4 days with daily monitoring of Cx expression, Cx localization, and gap junction channel and hemichannel functionality. Gap junction activity was low shortly after isolation, whereas the inverse was observed for hemichannel functionality. Both channel types displayed high activity near the end stages of the cultivation period. The Cx32-to-Cx43 switch became progressively manifested at the translational level. At the transcriptional level, a fivefold decrease in Cx32 messenger RNA abundance and a twofold increase in Cx43 expression were noticed within the first 24 h of cultivation. Throughout the cultivation period, Cx32 was mainly located at the plasma membrane surface, whereas Cx43 immunostaining was more diffuse. Application of three Cx43 inhibitors resulted in the downregulation of both hemichannel functionality and gap junction activity. This was paralleled by decreased expression and activity of caspase 3 as well as by reduced expression of Bid. Collectively, these data show that Cx43 signaling actively contributes to the occurrence of spontaneous apoptosis in cultures of primary hepatocytes.},
  author       = {Vinken, Mathieu and Decrock, Elke and Vanhaecke, Tamara and Leybaert, Luc and Rogiers, Vera},
  issn         = {1096-6080},
  journal      = {TOXICOLOGICAL SCIENCES},
  keyword      = {primary hepatocyte,apoptosis,connexin43,hemichannel,gap junction,ADULT-RAT HEPATOCYTES,JUNCTIONAL INTERCELLULAR COMMUNICATION,LONG-TERM CULTURE,GAP-JUNCTION,MOLECULAR-MECHANISMS,CELL-PROLIFERATION,OVAL CELLS,EXPRESSION,LIVER,DIFFERENTIATION},
  language     = {eng},
  number       = {1},
  pages        = {175--186},
  title        = {Connexin43 signaling contributes to spontaneous apoptosis in cultures of primary hepatocytes},
  url          = {http://dx.doi.org/10.1093/toxsci/kfr277},
  volume       = {125},
  year         = {2012},
}

Chicago
Vinken, Mathieu, Elke Decrock, Tamara Vanhaecke, Luc Leybaert, and Vera Rogiers. 2012. “Connexin43 Signaling Contributes to Spontaneous Apoptosis in Cultures of Primary Hepatocytes.” Toxicological Sciences 125 (1): 175–186.
APA
Vinken, M., Decrock, E., Vanhaecke, T., Leybaert, L., & Rogiers, V. (2012). Connexin43 signaling contributes to spontaneous apoptosis in cultures of primary hepatocytes. TOXICOLOGICAL SCIENCES, 125(1), 175–186.
Vancouver
1.
Vinken M, Decrock E, Vanhaecke T, Leybaert L, Rogiers V. Connexin43 signaling contributes to spontaneous apoptosis in cultures of primary hepatocytes. TOXICOLOGICAL SCIENCES. 2012;125(1):175–86.
MLA
Vinken, Mathieu, Elke Decrock, Tamara Vanhaecke, et al. “Connexin43 Signaling Contributes to Spontaneous Apoptosis in Cultures of Primary Hepatocytes.” TOXICOLOGICAL SCIENCES 125.1 (2012): 175–186. Print.