Iron absorption from soybean ferritin in nonanemic women

Jeon

Proc. Natl. Acad. Sci. U.S.A.

et al. 2009

307

246

The most widespread dietary problem in the world is mineral deficiency. We used the nicotianamine synthase (NAS) gene to increase mineral contents in rice grains. Nicotianamine (NA) is a chelator of metals and a key component of metal homeostasis. We isolated activation-tagged mutant lines in which expression of a rice NAS gene, OsNAS3, was increased by introducing 35S enhancer elements. Shoots and roots of the OsNAS3 activationtagged plants (OsNAS3-D1) accumulated more Fe and Zn. Seeds from our OsNAS3-D1 plants grown on a paddy field contained elevated amounts of Fe (2.9-fold), Zn (2.2-fold), and Cu (1.7-fold). The NA level was increased 9.6-fold in OsNAS3-D1 seeds. Analysis by size exclusion chromatography coupled with inductively coupled plasma mass spectroscopy showed that WT and Os-NAS3-D1 seeds contained equal amounts of Fe bound to IP6, whereas OsNAS3-D1 had 7-fold more Fe bound to a low molecular mass, which was likely NA. Furthermore, this activation led to increased tolerance to Fe and Zn deficiencies and to excess metal (Zn, Cu, and Ni) toxicities. In contrast, disruption of OsNAS3 caused an opposite phenotype. To test the bioavailability of Fe, we fed anemic mice with either engineered or WT seeds for 4 weeks and measured their concentrations of hemoglobin and hematocrit. Mice fed with engineered seeds recovered to normal levels of hemoglobin and hematocrit within 2 weeks, whereas those that ate WT seeds remained anemic. Our results suggest that an increase in bioavailable mineral content in rice grains can be achieved by enhancing NAS expression. activation tagging ͉ bioavailability ͉ hemoglobin ͉ metal homeostasis

Section: Discussionmentioning

confidence: 99%

Iron fortification of rice seeds through activation of the nicotianamine synthase gene

Jeon

Proc. Natl. Acad. Sci. U.S.A.

et al. 2009

307

246

American Journal of Physiology-Gastrointestinal and Liver Physi

“…A third source of dietary iron is currently emerging: ferritin, a multisubunit protein containing caged iron (26,52,53). Indeed, a recent study demonstrated that ferritin iron is absorbed from the intestinal lumen by a process different from heme and inorganic iron absorption, and, once it is absorbed, it behaves as a slow-release iron donor (54).…”

mentioning

confidence: 99%

Endocytic pathway of exogenous iron-loaded ferritin in intestinal epithelial (Caco-2) cells

Antileo

Garri

Tapia

et al. 2013

Artículo de publicación ISIFerritin, a food constituent of animal and vegetal origin, is a source of dietary iron. Its hollow central cavity has the capacity to store up to 4,500 atoms of iron, so its potential as an iron donor is advantageous to heme iron, present in animal meats and inorganic iron of mineral or vegetal origin. In intestinal cells, ferritin internalization by endocytosis results in the release of its iron into the cytosolic labile iron pool. The aim of this study was to characterize the endocytic pathway of exogenous ferritin absorbed from the apical membrane of intestinal epithelium Caco-2 cells, using both transmission electron microscopy and fluorescence confocal microscopy. Confocal microscopy revealed that endocytosis of exogenous AlexaFluor 488-labeled ferritin was initiated by its engulfment by clathrin-coated pits and internalization into early endosomes, as determined by codistribution with clathrin and early endosome antigen 1 (EEA1). AlexaFluor 488-labeled ferritin also codistributed with the autophagosome marker microtubule-associated protein 1 light chain 3 (LC3) and the lysosome marker lysosomal-associated membrane protein 2 (LAMP2). Transmission electron microscopy revealed that exogenously added ferritin was captured in plasmalemmal pits, double-membrane compartments, and multivesicular bodies considered as autophagosomes and lysosomes. Biochemical experiments revealed that the lysosome inhibitor chloroquine and the autophagosome inhibitor 3-methyladenine (3-MA) inhibited degradation of exogenously added 131I-labeled ferritin. This evidence is consistent with a model in which exogenous ferritin is internalized from the apical membrane through clathrin-coated pits, and then follows a degradation pathway consisting of the passage through early endosomes, autophagosomes, and autolysosomes.This work was financed by project ICM-P05-001-F from the Millennium Scientific Initiative, Ministerio de Economía, Chile (to M. T. Núñez), and by Grants 1070840 from Fondo Nacional de Ciencia y Tecnología (to M. T. Núñez) and ACT 1111 (to S. Lavandero and M. Chiong)

“…Animal models used for nutritional studies Many nutritional studies related to iron are performed in humans (Beach et al, 2003;Troost et al, 2003;Lonnerdal et al, 2006). Nevertheless, human research in basic metabolism is expensive and difficult to perform accurately.…”

Section: Common Methods Used In Fe Metabolismmentioning

confidence: 99%

“…There are many studies available in the scientific literature about iron absorption and regulation. Iron supplementation studies determine factors that affect iron absorption and oxidative damage (Beach et al, 2003;Casanueva and Viteri, 2003;Troost et al, 2003;Lonnerdal et al, 2006;Nagababu et al, 2008;Jin et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: a review

García¹,

Díaz-Castro

2013

Animal

Iron deficiency is the most common nutritional deficiency in the world. Special molecules have evolved for iron acquisition, transport and storage in soluble, nontoxic forms. Studies about the effects of iron on health are focused on iron metabolism or nutrition to prevent or treat iron deficiency and anemia. These studies are focused in two main aspects: (1) basic studies to elucidate iron metabolism and (2) nutritional studies to evaluate the efficacy of iron supplementation to prevent or treat iron deficiency and anemia. This paper reviews the advantages and disadvantages of the experimental models commonly used as well as the methods that are more used in studies related to iron. In vitro studies have used different parts of the gut. In vivo studies are done in humans and animals such as mice, rats, pigs and monkeys. Iron metabolism is a complex process that includes interactions at the systemic level. In vitro studies, despite physiological differences to humans, are useful to increase knowledge related to this essential micronutrient. Isotopic techniques are the most recommended in studies related to iron, but their high cost and required logistic, making them difficult to use. The depletion--repletion of hemoglobin is a method commonly used in animal studies. Three depletion--repletion techniques are mostly used: hemoglobin regeneration efficiency, relative biological values (RBV) and metabolic balance, which are official methods of the association of official analytical chemists. These techniques are well-validated to be used as studies related to iron and their results can be extrapolated to humans. Knowledge about the main advantages and disadvantages of the in vitro and animal models, and methods used in these studies, could increase confidence of researchers in the experimental results with less costs.