Projecten per jaar
Samenvatting
Background and aims: Being goalkeepers of liver homeostasis, gap junctions are also
involved in hepatotoxicity. However, their role in this process is ambiguous, as gap junctions
can act as both targets and effectors of liver toxicity. This particularly holds true for druginduced
liver insults. In the present study, the role and functional relevance of connexin32 and
connexin43, the building stones of liver gap junctions, were investigated in acetaminopheninduced
hepatotoxicity. Methods: C57BL/6 mice were overdosed with acetaminophen
followed by analysis of the expression and localization of connexins as well as monitoring of
hepatic gap junction functionality. Furthermore, acetaminophen-induced liver injury was
compared between mice genetically deficient in either connexin32 or connexin43 and wild type animals. Evaluation of the toxicological response was based on a set of clinically
relevant parameters, including protein adduct formation, histopathological examination,
measurement of alanine aminotransferase, cytokines, reduced and oxidized glutathione, and
analysis of proliferating cell nuclear antigen expression. Results: It was found that gap
junction communication deteriorates upon acetaminophen intoxication in wild type mice,
which was associated with a switch in mRNA and protein production from connexin32 to
connexin43. Furthermore, connexin43-deficient animals showed increased liver cell death,
inflammation and oxidative stress in comparison with wild type counterparts, whereas the
opposite seems to hold true for mice lacking connexin32. Conclusion: These results suggest
that hepatic connexin43-based signaling protects against acetaminophen-induced liver
toxicity.
Originele taal-2 | English |
---|---|
Artikelnummer | 586 |
Pagina's (van-tot) | 500A-500A |
Tijdschrift | Hepatology |
Volume | 62 |
Nummer van het tijdschrift | SI |
Status | Published - 1 okt 2015 |
Evenement | The Liver Meeting 2015 from the American Association for the Study of Liver Diseases - San Francisco, United States Duur: 13 nov 2015 → 17 nov 2015 |
Vingerafdruk
Duik in de onderzoeksthema's van 'Protective effects of connexin43 signaling in acetaminophen-induced liver injury'. Samen vormen ze een unieke vingerafdruk.Projecten
- 5 Afgelopen
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OZR2813: Bilaterale samenwerking ikv gemeenschappelijke doctoraatsproject: Bench Fee voor Joint PhD VUB-Universidade de Sao Paulo, Michael Maes
10/06/15 → 31/07/17
Project: Fundamenteel
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Onderzoekersoutput
- 1 Article
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Involvement of connexin43 in acetaminophen-induced liver injury
Maes, M., Mcgill, M. R., da Silva, T. C., Abels, C., Lebofsky, M., Monteiro de Araújo, C. M., Tiburcio, T., Alves Pereira, I. V., Willebrords, J., Crespo Yanguas, S., Farhood, A., Beschin, A., Van Ginderachter, J., Zaidan Dagli, M. L., Jaeschke, H., Cogliati, B. & Vinken, M., 1 jun 2016, In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 1862, 6, blz. 1111-1121 11 blz.Onderzoeksoutput: Article › peer review
31 Citaten (Scopus)
Activiteiten
- 1 Participation in conference
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The Liver Meeting 2015 from the American Association for the Study of Liver Diseases
Michaël Maes (Participant)
13 nov 2015 → 17 nov 2015Activiteit: Participation in conference