Journal
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
Volume 109, Issue 3, Pages 164-174Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1742-7843.2011.00702.x
Keywords
-
Categories
Funding
- European Union [BIO2-CT-93-0471]
- Research Training Network 'Nutritional and Environmental Nuclear Receptor Modulators: Transcriptional Pathways to Abnormal Development and Cancer' [RTN2-2001-00370, HPRN-CT-2002-00268]
- Danish Biotechnology program
- Agnes and Poul Friis Foundation
- Danish Research School in Molecular Cancer Research
- Fabrikant Einar Willumsens Mindelegat
- Fonden Victoria og Henry Andersens Legat
- Th. Maigaards Eftf. Fru Lily Benthine Lunds Fond
- Civilingenior Bent Bogh og hustru Inge Boghs Fond
- Else og Mogens Wedell-Wedellsborgs Fond
- Anders Hasselbalchs Fond til Leukaemiens Bekaempelse
Ask authors/readers for more resources
Valproic acid (VPA) is a known teratogen. In the present study, the effects of VPA and seven VPA derivatives with different teratogenic potencies (isobutyl-, 5-methyl-, ethyl-, propyl-, butyl-, pentyl- and hexyl-4-yn-VPA) were investigated in L929 cells in vitro. Evaluated end-points included changes in cell proliferation, growth, cell cycle distribution, morphology, speed, glycogen synthase kinase-3 beta (GSK-3 beta) and Erk1/2 phosphorylation, and histone H3 acetylation. Changes in proliferation, growth, speed, Erk1/2 and GSK-3 beta-Tyr216 phosphorylation, and H3 acetylation were significantly associated with the teratogenic potencies of the VPA derivatives. However, in contrast to changes in Erk1/2 phosphorylation and H3 acetylation, significant changes in GSK-3 beta phosphorylation could only be obtained in response to prolonged incubation at high drug concentration. There was an association between changes in H3 acetylation and GSK-3 beta-Tyr216 phosphorylation, whereas none of these end-points were associated with changes in Erk1/2 phosphorylation. These results suggest that the teratogenic potencies of VPA and VPA derivatives are related to effects on both Erk1/2 and histone deacetylase activities, whereas changes in GSK-3 beta activity are possibly a secondary effect.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available