Neural tube closure depends on nitric oxide synthase activity

• Published in: Journal of neurochemistry Vol. 96; no. 1; pp. 247 - 253
• Main Authors: Nachmany, Amir, Gold, Veronica, Tsur, Asaf, Arad, Dan, Weil, Miguel
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2006; Blackwell; Blackwell Publishing Ltd
• Subjects: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - antagonists & inhibitors; Ageing, cell death; Animals; Biological and medical sciences; Biopterins - analogs & derivatives; Biopterins - pharmacology; Calcimycin - pharmacology; Calmodulin - antagonists & inhibitors; Cell physiology; Chick Embryo; Embryos; Enzyme Inhibitors - pharmacology; Fatty Acids - metabolism; Fluorescein; Fluorescent Dyes; folate pathway; Fundamental and applied biological sciences. Psychology; Imidazoles - pharmacology; Indicators and Reagents; Inhibitor drugs; Isolated neuron and nerve. Neuroglia; methionine synthase; Molecular and cellular biology; neural tube; Neural Tube Defects - enzymology; Neural Tube Defects - genetics; Neurology; Nitric oxide; Nitric Oxide Donors - pharmacology; nitric oxide synthase; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type I - physiology; Nitroprusside - pharmacology; Vertebrates: nervous system and sense organs; Vitamin B 12 - metabolism; O-Acetylhomoserine (thiol)-lyase; Embryo; Calcium; Enzyme; methionine synthase; neural tube; Lyases; Biosynthesis; Folic acid; Folate; Nitric-oxide synthase; folate pathway; Vertebrata; Endogenous; Nitric oxide; Chicken; Oxidoreductases; Ionophore; nitric oxide synthase; Aves; chick embryo; Carbon-oxygen lyases; Calmodulin
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03542.x

Summary Neural tube (NT) closure is a multifactorial process that involves yet unresolved molecular mechanisms. It had been shown previously that high levels of nitric oxide (NO) block the process of NT closure in the chick embryo by inhibiting methionine synthase (MS). The MS inhibition and its effect on NT closure could be alleviated by folic acid, suggesting the involvement of the folate–methionine pathway in the process. Here we test the hypothesis that endogenous nitric oxide synthase (NOS) activity regulates the MS activity required in the process of NT closure. The experiments described here reveal that NOS activity per se, is indeed critical for NT closure in the chick embryo. Inhibition of NOS activity with either 2,4‐diamino‐6‐hydroxypyrimidine (DAHP), which blocks biosynthesis of the NOS co‐factor tetrahydrobiopterin (BH4), or with calmidazolium, which blocks calcium–calmodulin binding to NOS, resulted in reduced MS activity and consequently ablated NT closure. Addition of BH4 or the calcium ionophore A23187 restored NOS and MS activities, resulting in NT closure. The results described here imply that NOS and MS activities can serve as functional markers in this developmental process as they are essential in the process of NT closure.