The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities. / Gotfryd, Kamil; Hansen, Maria; Kawa, Anna; Ellerbeck, Ursula; Nau, Heinz; Berezin, Vladimir; Bock, Elisabeth; Walmod, Peter S.

In: Basic & Clinical Pharmacology & Toxicology Online, Vol. 109, No. 3, 25.03.2011, p. 164-174.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gotfryd, K, Hansen, M, Kawa, A, Ellerbeck, U, Nau, H, Berezin, V, Bock, E & Walmod, PS 2011, 'The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities', Basic & Clinical Pharmacology & Toxicology Online, vol. 109, no. 3, pp. 164-174. https://doi.org/10.1111/j.1742-7843.2011.00702.x

APA

Gotfryd, K., Hansen, M., Kawa, A., Ellerbeck, U., Nau, H., Berezin, V., Bock, E., & Walmod, P. S. (2011). The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities. Basic & Clinical Pharmacology & Toxicology Online, 109(3), 164-174. https://doi.org/10.1111/j.1742-7843.2011.00702.x

Vancouver

Gotfryd K, Hansen M, Kawa A, Ellerbeck U, Nau H, Berezin V et al. The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities. Basic & Clinical Pharmacology & Toxicology Online. 2011 Mar 25;109(3):164-174. https://doi.org/10.1111/j.1742-7843.2011.00702.x

Author

Gotfryd, Kamil ; Hansen, Maria ; Kawa, Anna ; Ellerbeck, Ursula ; Nau, Heinz ; Berezin, Vladimir ; Bock, Elisabeth ; Walmod, Peter S. / The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities. In: Basic & Clinical Pharmacology & Toxicology Online. 2011 ; Vol. 109, No. 3. pp. 164-174.

Bibtex

@article{520aea273d3240589626c7cc9c730295,
title = "The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities",
abstract = " 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{\ss} (GSK-3{\ss}) and Erk1/2 phosphorylation, and histone H3 acetylation. Changes in proliferation, growth, speed, Erk1/2 and GSK-3{\ss}-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{\ss} 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{\ss}-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{\ss} activity are possibly a secondary effect.",
author = "Kamil Gotfryd and Maria Hansen and Anna Kawa and Ursula Ellerbeck and Heinz Nau and Vladimir Berezin and Elisabeth Bock and Walmod, {Peter S}",
note = "{\textcopyright} 2011 The Authors. Basic & Clinical Pharmacology & Toxicology {\textcopyright} 2011 Nordic Pharmacological Society.",
year = "2011",
month = mar,
day = "25",
doi = "10.1111/j.1742-7843.2011.00702.x",
language = "English",
volume = "109",
pages = "164--174",
journal = "Basic and Clinical Pharmacology and Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities

AU - Gotfryd, Kamil

AU - Hansen, Maria

AU - Kawa, Anna

AU - Ellerbeck, Ursula

AU - Nau, Heinz

AU - Berezin, Vladimir

AU - Bock, Elisabeth

AU - Walmod, Peter S

N1 - © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

PY - 2011/3/25

Y1 - 2011/3/25

N2 - 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-3ß (GSK-3ß) and Erk1/2 phosphorylation, and histone H3 acetylation. Changes in proliferation, growth, speed, Erk1/2 and GSK-3ß-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-3ß 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-3ß-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-3ß activity are possibly a secondary effect.

AB - 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-3ß (GSK-3ß) and Erk1/2 phosphorylation, and histone H3 acetylation. Changes in proliferation, growth, speed, Erk1/2 and GSK-3ß-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-3ß 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-3ß-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-3ß activity are possibly a secondary effect.

U2 - 10.1111/j.1742-7843.2011.00702.x

DO - 10.1111/j.1742-7843.2011.00702.x

M3 - Journal article

C2 - 21439023

VL - 109

SP - 164

EP - 174

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 3

ER -

ID: 33815297