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Title: Proteomic and metabolomic responses to connexin43 silencing in primary hepatocyte cultures
Authors: Vinken, Mathieu
Maes, Michael
Cavill, Rachel
Ellis, James K.
Decrock, Elke
Leybaert, Luc
Staes, An
Gevaert, Kris
Oliveira, Andre G.
Menezes, Gustavo B.
Cogliati, Bruno
Zaidan Dagli, Maria Lucia
Ebbels, Timothy M. D.
Witters, Erwin
Keun, Hector C.
Vanhaecke, Tamara
Rogiers, Vera
Issue Date: 2013
Source: ARCHIVES OF TOXICOLOGY, 87 (5), p. 883-894
Abstract: Freshly established cultures of primary hepatocytes progressively adopt a foetal-like phenotype and display increased production of connexin43. The latter is a multifaceted cellular entity with variable subcellular locations, including the mitochondrial compartment. Cx43 forms hemichannels and gap junctions that are involved in a plethora of physiological and pathological processes, such as apoptosis. The present study was conducted with the goal of shedding more light onto the role of connexin43 in primary hepatocyte cultures. Connexin43 expression was suppressed by means of RNA interference technology, and the overall outcome of this treatment on the hepatocellular proteome and metabolome was investigated using tandem mass tag-based differential protein profiling and H-1 NMR spectroscopy, respectively. Global protein profiling revealed a number of targets of the connexin43 knock-down procedure, including mitochondrial proteins (heat shock protein 60, glucose-regulated protein 75, thiosulphate sulphurtransferase and adenosine triphosphate synthase) and detoxifying enzymes (glutathione S-transferase mu 2 and cytochrome P450 2C70). At the metabolomic level, connexin43 silencing caused no overt changes, though there was some evidence for a subtle increase in intracellular glycine quantities. Collectively, these data could further substantiate the established existence of a mitochondrial connexin pool and could be reconciled with the previously reported involvement of connexin43 signalling in spontaneously occurring apoptosis in primary hepatocyte cultures.
Notes: Vinken, M (reprint author),Vrije Univ Brussel, Pharmaceut Res Ctr, Fac Med & Pharm, Dept Toxicol, B-1090 Brussels, Belgium. Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Fac Med, London SW7 2AZ, England. Vlaamse Instelling Technol Onderzoek, B-2400 Mol, Belgium. Univ Antwerp, Dept Biol, B-2020 Antwerp, Belgium. Univ Antwerp, Ctr Prote, B-2020 Antwerp, Belgium. Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, B-3590 Diepenbeek, Belgium. Univ Ghent, Fac Med & Hlth Sci, Physiol Grp, Dept Basic Med Sci, B-9000 Ghent, Belgium. Vlaams Inst Biotechnol, Dept Med Prot Res, B-9000 Ghent, Belgium. Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium. Univ Fed Minas Gerais, Dept Morphol, Inst Biol Sci, Belo Horizonte, MG, Brazil. Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Sao Paulo, Brazil.
Keywords: Toxicology;Primary hepatocyte; Connexin43; Proteomics; Metabolomics
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ISSN: 0340-5761
e-ISSN: 1432-0738
DOI: 10.1007/s00204-012-0994-0
ISI #: 000317682700011
Category: A1
Type: Journal Contribution
Validations: ecoom 2014
Appears in Collections:Research publications

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