Abstract | BACKGROUND:
Iron is finely regulated due to its vital roles in organisms and the peroxidase reactivity if excess. Solute Carrier Family 46 Member 1 (SLC46A1), also named PCFT or HCP1, is the main importer of heme‑iron in the intestine, but has a high abundance in the liver. Since the liver has a central role in iron homeostasis, whether SLC46A1 regulates hepatic iron metabolism is of interest to be identified. METHODS: The recombinant adeno-associated virus vectors were used to hepatic-specifically inhibit SLC46A1 expression to observe its effects on hepatic iron metabolism. Then the abilities of SLC46A1 in importing heme and folate, and consequent alterations of iron content in hepatocytes were determined. Furthermore, effects of iron on SLC46A1 expression were investigated both in vitro and in vivo. RESULTS: The hepatocyte-specific inhibition of SLC46A1 decreases iron content in the liver and increases iron content in serum. Expressions of iron-related molecules, transferrin receptor 1, hepcidin and ferroportin, are correspondingly altered. Interestingly, free heme concentration in serum is increased, indicating a decreased import of heme by the liver. In hepatocytes, SLC46A1 is capable of importing hemin, increasing intracellular iron content. The import of hemin by SLC46A1 is unaffected by its other substrate, folate. Instead, hemin treatment decreases SLC46A1 expression, reducing the import of folate. In addition, SLC46A1 itself shows to be iron-responsive both in vivo and in vitro, making it available for regulating iron metabolism. CONCLUSION:
|
Authors | Hongxia Li, Dongyao Wang, Huiwen Wu, Hui Shen, Diya Lv, Yinyin Zhang, Hongtao Lu, Jianxin Yang, Yuxiao Tang, Min Li |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 110
Pg. 154306
(09 2020)
ISSN: 1532-8600 [Electronic] United States |
PMID | 32621820
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- Proton-Coupled Folate Transporter
- SLC46A1 protein, human
- Slc46a1 protein, mouse
- Heme
- Hemin
- Iron
|
Topics |
- Animals
- Cells, Cultured
- Heme
(metabolism)
- Hemin
(metabolism)
- Hepatocytes
(metabolism)
- Humans
- Iron
(metabolism)
- Liver
(metabolism)
- Mice
- Mice, Inbred C57BL
- Proton-Coupled Folate Transporter
(antagonists & inhibitors, physiology)
|