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http://purl.uniprot.org/citations/24747731http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Folate is an essential nutrient for cell survival and embryogenesis. 10-Formyltetrahydrofolate dehydrogenase (FDH) is the most abundant folate enzyme in folate-mediated one-carbon metabolism. 10-Formyltetrahydrofolate dehydrogenase converts 10-formyltetrahydrofolate to tetrahydrofolate and CO2, the only pathway responsible for formate oxidation in methanol intoxication. 10-Formyltetrahydrofolate dehydrogenase has been considered a potential chemotherapeutic target because it was down-regulated in cancer cells. However, the normal physiological significance of 10-Formyltetrahydrofolate dehydrogenase is not completely understood, hampering the development of therapeutic drug/regimen targeting 10-Formyltetrahydrofolate dehydrogenase.

Methods

10-Formyltetrahydrofolate dehydrogenase expression in zebrafish embryos was knocked-down using morpholino oligonucleotides. The morphological and biochemical characteristics of fdh morphants were examined using specific dye staining and whole-mount in-situ hybridization. Embryonic folate contents were determined by HPLC.

Results

The expression of 10-formyltetrahydrofolate dehydrogenase was consistent in whole embryos during early embryogenesis and became tissue-specific in later stages. Knocking-down fdh impeded morphogenetic movement and caused incorrect cardiac positioning, defective hematopoiesis, notochordmalformation and ultimate death of morphants. Obstructed F-actin polymerization and delayed epiboly were observed in fdh morphants. These abnormalities were reversed either by adding tetrahydrofolate or antioxidant or by co-injecting the mRNA encoding 10-formyltetrahydrofolate dehydrogenase N-terminal domain, supporting the anti-oxidative activity of 10-formyltetrahydrofolate dehydrogenase and the in vivo function of tetrahydrofolate conservation for 10-formyltetrahydrofolate dehydrogenase N-terminal domain.

Conclusions

10-Formyltetrahydrofolate dehydrogenase functioned in conserving the unstable tetrahydrofolate and contributing to the intracellular anti-oxidative capacity of embryos, which was crucial in promoting proper cell migration during embryogenesis.

General significance

These newly reported tetrahydrofolate conserving and anti-oxidative activities of 10-formyltetrahydrofolate dehydrogenase shall be important for unraveling 10-formyltetrahydrofolate dehydrogenase biological significance and the drug development targeting 10-formyltetrahydrofolate dehydrogenase."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.org/dc/terms/identifier"doi:10.1016/j.bbagen.2014.04.009"xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Chen Y.H."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Lin C.Y."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Lee G.H."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Tsai H.J."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Fu T.F."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Tsai J.N."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Chen B.H."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Hsiao T.H."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Wu H.R."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Chang W.N."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/author"Kao T.T."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/name"Biochim Biophys Acta"xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/pages"2340-2350"xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/title"Knocking down 10-Formyltetrahydrofolate dehydrogenase increased oxidative stress and impeded zebrafish embryogenesis by obstructing morphogenetic movement."xsd:string
http://purl.uniprot.org/citations/24747731http://purl.uniprot.org/core/volume"1840"xsd:string
http://purl.uniprot.org/citations/24747731http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24747731
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