Folate Dotaz Zobrazit nápovědu
Increased levels of plasma cysteine are associated with obesity and metabolic disturbances. Our recent genetic analyses in spontaneously hypertensive rats (SHR) revealed a mutated Folr1 (folate receptor 1) as the quantitative trait gene associated with diminished renal Folr1 expression, lower plasma folate levels, hypercysteinemia, hyperhomocysteinemia and metabolic disturbances. To further analyse the effects of the Folr1 gene expression on folate metabolism, we used mass spectrometry to quantify folate profiles in the plasma and liver of an SHR-1 congenic strain, with wild type Folr1 allele on the SHR genetic background, and compared them with the SHR strain. In the plasma, concentration of 5-methyltetrahydrofolate (5mTHF) was significantly higher in SHR-1 congenic rats compared to SHR (60+/-6 vs. 42+/-2 nmol/l, P<0.01) and 5mTHF monoglutamate was the predominant form in both strains (>99 % of total folate). In the liver, SHR-1 congenic rats showed a significantly increased level of 5mTHF and decreased concentrations of dihydrofolate (DHF), tetrahydrofolate (THF) and formyl-THF when compared to the SHR strain. We also analysed the extent of folate glutamylation in the liver. Compared with the SHR strain, congenic wild-type Folr1 rats had significantly higher levels of 5mTHF monoglutamate. On the other hand, 5mTHF penta- and hexaglutamates were significantly higher in SHR when compared to SHR-1 rats. This inverse relationship of rat hepatic folate polyglutamate chain length and folate sufficiency was also true for other folate species. These results strongly indicate that the whole body homeostasis of folates is substantially impaired in SHR rats compared to the SHR-1 congenic strain and might be contributing to the associated metabolic disturbances observed in our previous studies.
V letošním květovém čísle Clinical Chemistry vyšla obšírná práce amerických autorů Christine M. Pfeiffer et al. zabývající se hladinami celkového plazmatického homocysteinu (Trends in circulating concentrations of total homocysteine among US adolescents and adults: Findings from the 1991–1994 and 1999–2004 National Health and Nutrition Examination Surveys). V rámci rozsáhlých a opakovaných studií autoři stanovovali homocystein ve vzorcích od reprezentativních souborů osob před fortifi kací potravy folátem a opakovaně i po zavedení povinné fortifi kace. V úvodu stejného čísla Clinical Chemistry otiskli norští autoři Per Magne Ueland a Steinar Hustad (University Bergen a Haukeland University Hospital Bergen) k této problematice editorial, vysvětlující pozadí fortifi kace folátem v USA a Kanadě, který hodnotí výsledky studií popsaných nejen v uvedené práci a kriticky zvažuje možné negativní důsledky fortifi kace (Homocysteine and folate status in an era of folic acid fortifi cation: Balancing benefi ts, risks, and B-vitamins. Clinical Chemistry 54, 2008, 5, p. 779–781). V tomto sdělení je stručný komentovaný výtah z obou článků.
In the issue No. 5 of Clinical Chemistry from May 2008 an extensive article was published by Christine M. Pfeiffer et al. dealing with total homocysteine levels in plasma (Trends in circulating concentrations of total homocysteine among US adolescents and adults: Findings from the 1991–1994 and 1999–2004 National Health and Nutrition Examination Surveys. Clinical Chemistry 54, 2008, 5, p. 801–813). Within the large and repeated trials on representative cohorts of patients total homocysteine was estimated prior to and after the introduction of mandatory fortifi cation of food with folate. An editorial was published in the same issue of Clinical Chemistry by Norwegian authors Per Magne Ueland and Steinar Hustad (University Bergen and Haukeland University Hospital Bergen) explaining the background of folate fortifi cation in the USA and Canada, evaluating results of the trials mentioned above and considering criticaly possible adverse effects of folate fortifi cation (Homocysteine and folate status in an era of folic acid fortifi cation: Balancing benefi ts, risks, and B-vitamins. Clinical Chemistry 54, 2008, 5, p. 779–781). In this contribution we present a short and commented extract of both articles.
- MeSH
- defekty neurální trubice prevence a kontrola MeSH
- fortifikované potraviny MeSH
- homocystein krev účinky léků MeSH
- hyperhomocysteinemie prevence a kontrola MeSH
- kyselina listová aplikace a dávkování metabolismus MeSH
- lidé MeSH
- potravní doplňky MeSH
- vitamin B 12 aplikace a dávkování metabolismus MeSH
- Check Tag
- lidé MeSH
Folate, also known as vitamin B9, is necessary for essential cellular functions such as DNA synthesis, repair, and methylation. It is supplied to the cell via several transporters and receptors, including folate receptor (FR) β, a GPI-anchored protein belonging to the folate receptor family. As FRβ shows a restricted expression to cells of myeloid origin and only a subset of activated macrophages and placental cells have been shown to express functional FRβ, it represents a promising target for future therapeutic strategies. In this study, we performed affinity purification and mass spectrometric analysis of the protein microenvironment of FRβ in the plasma membrane of human FRβ(+) macrophages and FRβ-transduced monocytic THP-1 cells. In this manner, we identified a novel role of FRβ: that is, we report functional interactions of FRβ with receptors mediating cellular adhesion, in particular the CD11b/CD18 β2 integrin heterodimer complement receptor type 3/Mac-1. This interaction results in impeded adhesion of FRβ(+) human primary macrophages and THP-1 cells to collagen in comparison with their FRβ(-) counterparts. We further show that FRβ is only expressed by human macrophages when differentiated with M-CSF. These findings thus identify FRβ as a novel CD11b/CD18 regulator for trafficking and homing of a subset of macrophages on collagen.
- MeSH
- antigeny CD11b fyziologie MeSH
- antigeny CD18 fyziologie MeSH
- buněčná adheze MeSH
- folátový receptor 2 fyziologie MeSH
- kolagen farmakologie MeSH
- kultivované buňky MeSH
- kyselina listová metabolismus MeSH
- lidé MeSH
- makrofágy fyziologie MeSH
- pohyb buněk MeSH
- proliferace buněk MeSH
- tetradekanoylforbolacetát farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Folic acid (vitamin B9) rich sources are leafy green vegetables, legumes, whole grains, egg yolk, liver, and citrus fruit. In winter and early spring, there could be insufficient supply of vegetables and fruit and thus lower intake of folic acid and possible deficient folic acid blood concentrations. The aim of the study was to assess serum vitamin B9 concentrations depending on the season (the last third of winter - March, the last third of spring - May/June and the beginning of autumn - September) and different nutritional habits (apparently healthy adults non-smoking, non-obese 366 subjects; 204 persons of general population on traditional mixed diet; and 162 long-term lacto-ovo vegetarians). In general population group, the mean concentration of folate in March was low (narrowly above lower reference limit) with high incidence of deficient values - 31.5%. In May/ June vs. March was folate concentration significantly higher with deficient values in 13.2% of individuals. The highest serum values were observed in September with 11.1% of deficient values. In vegetarian vs. non-vegetarian group, significantly higher folate concentrations were found in each season with no deficient values. Folate and vitamin B12 are the regulators of homocysteinemia; plant food lacks of vitamin B12. The deficient folate serum values in March caused the mild hyperhomocysteinemia in 12.3% of individuals vs. only 5.9% and 4.8% of subjects in groups investigated in May/June and September. In spite of high folate concentrations in all investigations and no deficient value, 19.6-22.8% of vegetarians suffer from mild hyperhomocysteinemia as a consequence of deficient vitamin B12 concentrations in one quarter of subjects. As far as the general population is concerned, our findings suggest that winter and early spring are critical seasons in regards to optimal serum folate concentrations.
- MeSH
- dieta * MeSH
- dospělí MeSH
- kyselina listová krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- průzkumy a dotazníky MeSH
- roční období * MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
Handbook of experimental pharmacology, ISSN 0171-2004 volume 64
457 s. : il., tab.
- MeSH
- kyselina listová metabolismus MeSH
- sulfamethoxazol farmakologie MeSH
- trimethoprim farmakologie MeSH
- Publikační typ
- příručky MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- farmacie a farmakologie
- vnitřní lékařství
- Klíčová slova
- deficit cerebrálního folátu, 5-MTHF (5-methyltetrahydrofolát),
- MeSH
- autistická porucha diagnóza etiologie MeSH
- dítě MeSH
- folátové receptory zakotvené GPI * metabolismus nedostatek MeSH
- lidé MeSH
- mozkomíšní mok cytologie metabolismus MeSH
- nedostatek kyseliny listové MeSH
- neurodegenerativní nemoci etiologie terapie MeSH
- poruchy autistického spektra * diagnóza etiologie MeSH
- transportéry kyseliny listové metabolismus nedostatek MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Micronutrient deficiency conditions, such as anemia, are the most prevalent global health problem due to inadequate iron and folate in dietary sources. Biofortification advancements can propel the rapid amelioration of nutritionally beneficial components in crops that are required to combat the adverse effects of micronutrient deficiencies on human health. To date, several strategies have been proposed to increase micronutrients in plants to improve food quality, but very few approaches have intrigued `clustered regularly interspaced short palindromic repeats' (CRISPR) modules for the enhancement of iron and folate concentration in the edible parts of plants. In this review, we discuss two important approaches to simultaneously enhance the bioavailability of iron and folate concentrations in rice endosperms by utilizing advanced CRISPR-Cas9-based technology. This includes the 'tuning of cis-elements' and 'enhancer re-shuffling' in the regulatory components of genes that play a vital role in iron and folate biosynthesis/transportation pathways. In particular, base-editing and enhancer re-installation in native promoters of selected genes can lead to enhanced accumulation of iron and folate levels in the rice endosperm. The re-distribution of micronutrients in specific plant organs can be made possible using the above-mentioned contemporary approaches. Overall, the present review discusses the possible approaches for synchronized iron and folate biofortification through modification in regulatory gene circuits employing CRISPR-Cas9 technology.
- MeSH
- biofortifikace * MeSH
- CRISPR-Cas systémy * MeSH
- editace genu metody MeSH
- geneticky modifikované rostliny * metabolismus genetika MeSH
- kyselina listová * metabolismus MeSH
- lidé MeSH
- rýže (rod) metabolismus genetika MeSH
- železo * metabolismus MeSH
- zemědělské plodiny * metabolismus genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
