Separate pathways for cellular uptake of ferric and ferrous iron

被引:106
作者
Conrad, ME [1 ]
Umbreit, JN
Moore, EG
Hainsworth, LN
Porubcin, M
Simovich, MJ
Nakada, MT
Dolan, K
Garrick, MD
机构
[1] Univ S Alabama, USA Canc Ctr, Mobile, AL 36688 USA
[2] Centocor Inc, Malvern, PA 19355 USA
[3] SUNY Buffalo, Dept Biochem & Pediat, Buffalo, NY 14214 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2000年 / 279卷 / 04期
关键词
mobilferrin; calreticulin; integrin; divalent metal transporter-1; Nramp-2;
D O I
10.1152/ajpgi.2000.279.4.G767
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Separate pathways for transport of nontransferrin ferric and ferrous iron into tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway was shared with either zinc or copper. Manganese shared the ferrous pathway but had no effect on cellular uptake of ferric iron. We postulate that ferric iron was transported into cells via beta(3)-integrin and mobilferrin (IMP), whereas ferrous iron uptake was facilitated by divalent metal transporter-1 (DMT-1; Nramp-2). These conclusions were documented by competitive inhibition studies, utilization of a beta(3)-integrin antibody that blocked uptake of ferric but not ferrous iron, development of an anti-DMT-1 antibody that blocked ferrous iron and manganese uptake but not ferric iron, transfection of DMT-1 DNA into tissue culture cells that showed enhanced uptake of ferrous iron and manganese but neither ferric iron nor zinc, hepatic metal concentrations in mk mice showing decreased iron and manganese but not zinc or copper, and data showing that the addition of reducing agents to tissue culture media altered iron binding to proteins of the IMP and DMT-1 pathways. Although these experiments show ferric and ferrous iron can enter cells via different pathways, they do not indicate which pathway is dominant in humans.
引用
收藏
页码:G767 / G774
页数:8
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