The Phosphorylation State of GSK3β Serine 9 Correlated to the Development of Valproic Acid-Associated Fetal Cardiac Teratogenicity, Fetal VPA Syndrome, Rescued by Folic Acid Administration

Cardiovascular Toxicology
Wei-Hsuan YuHorng-Huei Liou

Abstract

The effects of the phosphorylation state of the glycogen synthase kinase 3β involved in the cardiac myocytes (jelly-like cells) epithelial-mesenchymal transition-associated migration during heart-valve formation were examined through the valproic acid-induced cardiac teratogenicity of transgenic line A34 of Tg in a the Brachydanio rerio embryo model. Valproic acid is an effective anti-epileptic drug; however, when taken by pregnant women to treat epilepsy, it can produce cardiac developmental defects in fetuses. In this study, the role of glycogen synthase kinase 3β in valproic acid-induced cardiac teratogenicity was investigated. Transgenic line A34 of zebrafish embryos was used at 3 days postfertilization. The results show that 78% (18/23) of the embryos treated with 0.10 mM valproic acid (group A) had incomplete chamber formation with normal looping and 22 % (5/23) had abnormal looping. Bradycardia was also found in comparison with control embryos (P < 0.001). For the embryos treated with 0.25 mM valproic acid (group B), 92% (22/24) demonstrated chamber formation failure and looping abnormality. Pericardial effusion, noncontracting ventricles, and enlarged, slowly beating atriums were observed at 6 days postfertilization. Va...Continue Reading

References

Oct 1, 1990·Journal of Clinical Psychopharmacology·R I Shader, D J Greenblatt
Oct 1, 1988·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·P E BinkerdA G Hendrickx
May 1, 1994·Circulation Research·M C Fishman, D Y Stainier
Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Apr 23, 2002·Nature Genetics·Amy J SehnertDidier Y R Stainier
Jun 1, 2002·Circulation Research·Stefan E Hardt, Junichi Sadoshima
Oct 29, 2002·Ultrasound in Medicine & Biology·Yi-Lwun HoFon-Jou Hsieh
Oct 29, 2002·Reproductive Toxicology·Leah C FullerDarrell J Wiens
Dec 14, 2002·Science·Kenneth D PossMark T Keating
Aug 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Angel RayaJuan Carlos Izpisúa-Belmonte
Sep 2, 2003·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Chiu-Ju HuangHuai-Jen Tsai
Nov 7, 2003·Development·Xiaodong ShuJau-Nian Chen
Mar 17, 2004·The Journal of Biological Chemistry·Ashour MichaelThomas Force
Aug 23, 2005·Toxicology and Applied Pharmacology·Jennifer E DawsonLouise M Winn
Sep 30, 2005·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Elena MenegolaErminio Giavini
Apr 14, 2006·Endocrine, Metabolic & Immune Disorders Drug Targets·Alberto VerrottiGiuseppe Latini
Feb 9, 2007·Birth Defects Research. Part A, Clinical and Molecular Teratology·Huiping ZhuRichard H Finnell
Dec 7, 2007·Journal of Obstetrics and Gynaecology Canada : JOGC = Journal D'obstétrique Et Gynécologie Du Canada : JOGC·R Douglas WilsonUNKNOWN MOTHERISK
Oct 3, 2008·The Journal of Clinical Investigation·Risto KerkelaGordon S Huggins
Mar 12, 2013·Pharmacology, Biochemistry, and Behavior·Silvia SintoniBarbara Monti
Aug 6, 2014·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Miki DozawaToshio Ohshima

❮ Previous
Next ❯

Citations

Aug 7, 2016·Nutrition & Metabolism·Xunxian Liu, Zemin Yao
Apr 20, 2017·International Journal of Molecular Sciences·Miaoyan ZhengHuan Liu
Oct 30, 2019·Current Neuropharmacology·Fan-Cheng KongMing-Kang Zhong
Jul 21, 2017·Current Psychiatry Reports·Dorothy GotlibMichelle Riba

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Cardiac Conduction System

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Discover the latest research on the cardiac conduction system here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Bradyarrhythmias

Bradyarrhythmias are slow heart rates. Symptoms may include syncope, dizziness, fatigure, shortness of breath, and chest pains. Find the latest research on bradyarrhythmias here.

Related Papers

British Medical Journal
C J BaileyF Harris
The Journal of Pediatrics
B DalensJ Gaulme
Zhonghua er ke za zhi. Chinese journal of pediatrics
Chun-hua GongShi-wei Yang
© 2022 Meta ULC. All rights reserved