Ferroportin deficiency impairs manganese metabolism in flatiron mice

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Young Ah Seo, Marianne Wessling-Resnick

Abstract

We examined the physiologic role of ferroportin (Fpn) in manganese (Mn) export using flatiron (ffe/+) mice, a genetic model of Fpn deficiency. Blood (0.0123 vs. 0.0107 mg/kg; P = 0.0003), hepatic (1.06 vs. 0.96 mg/kg; P = 0.0125), and bile Mn levels (79 vs. 38 mg/kg; P = 0.0204) were reduced in ffe/+ mice compared to +/+ controls. Erythrocyte Mn-superoxide dismutase was also reduced at 6 (0.154 vs. 0.096, P = 0.0101), 9 (0.131 vs. 0.089, P = 0.0162), and 16 weeks of age (0.170 vs. 0.090 units/mg protein/min; P < 0.0001). (54)Mn uptake after intragastric gavage was markedly reduced in ffe/+ mice (0.0187 vs. 0.0066% dose; P = 0.0243), while clearance of injected isotope was similar in ffe/+ and +/+ mice. These values were compared to intestinal absorption of (59)Fe, which was significantly reduced in ffe/+ mice (8.751 vs. 3.978% dose; P = 0.0458). The influence of the ffe mutation was examined in dopaminergic SH-SY5Y cells and human embryonic HEK293T cells. While expression of wild-type Fpn reversed Mn-induced cytotoxicity, ffe mutant H32R failed to confer protection. These combined results demonstrate that Fpn plays a central role in Mn transport and that flatiron mice provide an excellent genetic model to explore the role of th...Continue Reading

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Citations

Dec 24, 2015·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Young Ah SeoMarianne Wessling-Resnick
Nov 9, 2017·Frontiers in Molecular Neuroscience·Yong LiHong Jiang
May 25, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Khristy J ThompsonMarianne Wessling-Resnick
Sep 25, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eun-Kyung ChoiYoung Ah Seo
Sep 19, 2019·The Journal of Clinical Investigation·Courtney J MercadanteThomas B Bartnikas
Jul 13, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thibault CaveyOlivier Loréal
Sep 6, 2020·Molecular Neurobiology·Md Tanvir KabirMohamed M Abdel-Daim
Mar 20, 2019·Metallomics : Integrated Biometal Science·Lian JinGregory J Anderson
Jul 12, 2020·Journal of Alzheimer's Disease : JAD·Kelly M BakulskiSung Kyun Park
Aug 21, 2020·Learning & Memory·Jack T Rogers, Catherine M Cahill
Mar 18, 2020·Archives of Toxicology·Geir BjørklundJan Aaseth
Jun 18, 2017·Metallomics : Integrated Biometal Science·Qi YeJonghan Kim
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eun-Kyung ChoiYoung Ah Seo
Jan 8, 2021·Frontiers in Genetics·Young Ah SeoShigeki Iwase
Dec 2, 2020·Environmental Pollution·Ayaat T Hassan, Raymond W M Kwong
Apr 25, 2018·Molecular Genetics and Metabolism·Lance H RodanPankaj B Agrawal

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