Pea ferritin stability under gastric pH conditions determines the mechanism of iron uptake in Caco-2 cells

Perfecto, Antonio, Rodriguez-Ramiro, Ildefonso, Rodriguez-Celma, Jorge, Sharp, Paul, Balk, Janneke and Fairweather-Tait, Susan ORCID: https://orcid.org/0000-0002-1413-5569 (2018) Pea ferritin stability under gastric pH conditions determines the mechanism of iron uptake in Caco-2 cells. The Journal of Nutrition, 148 (8). 1229–1235. ISSN 0022-3166

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Abstract

Background: Iron deficiency is an enduring global health problem that requires new remedial approaches. Iron absorption from soybean-derived ferritin, an ∼550-kDa iron storage protein, is comparable to bioavailable ferrous sulfate (FeSO4). However, the absorption of ferritin is reported to involve an endocytic mechanism, independent of divalent metal ion transporter 1 (DMT-1), the transporter for nonheme iron. Objective: Our overall aim was to examine the potential of purified ferritin from peas (Pisum sativum) as a food supplement by measuring its stability under gastric pH treatment and the mechanisms of iron uptake into Caco-2 cells. Methods: Caco-2 cells were treated with native or gastric pH–treated pea ferritin in combination with dietary modulators of nonheme iron uptake, small interfering RNA targeting DMT-1, or chemical inhibitors of endocytosis. Cellular ferritin formation, a surrogate measure of iron uptake, and internalization of pea ferritin with the use of specific antibodies were measured. The production of reactive oxygen species (ROS) in response to equimolar concentrations of native pea ferritin and FeSO4 was also compared. Results: Pea ferritin exposed to gastric pH treatment was degraded, and the released iron was transported into Caco-2 cells by DMT-1. Inhibitors of DMT-1 and nonheme iron absorption reduced iron uptake by 26–40%. Conversely, in the absence of gastric pH treatment, the iron uptake of native pea ferritin was unaffected by inhibitors of nonheme iron absorption, and the protein was observed to be internalized in Caco-2 cells. Chlorpromazine (clathrin-mediated endocytosis inhibitor) reduced the native pea ferritin content within cells by ∼30%, which confirmed that the native pea ferritin was transported into cells via a clathrin-mediated endocytic pathway. In addition, 60% less ROS production resulted from native pea ferritin in comparison to FeSO4. Conclusion: With consideration that nonheme dietary inhibitors display no effect on iron uptake and the low oxidative potential relative to FeSO4, intact pea ferritin appears to be a promising iron supplement.

Item Type:	Article
Uncontrolled Keywords:	pea ferritin,phytoferritin,dmt-1,iron absorption,bioavailability,endocytosis
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Science > Research Groups > Molecular Microbiology Faculty of Science > Research Groups > Plant Sciences Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User:	Pure Connector
Date Deposited:	09 May 2018 14:30
Last Modified:	19 Oct 2023 02:12
URI:	https://ueaeprints.uea.ac.uk/id/eprint/66985
DOI:	10.1093/jn/nxy096

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