Identification of Zyklopen, a New Member of the Vertebrate Multicopper Ferroxidase Family, and Characterization in Rodents and Human Cells

被引:94
作者
Chen, Huijun [1 ,2 ]
Attieh, Zouhair K. [1 ,3 ]
Syed, Basharut A. [1 ,4 ]
Kuo, Yien-Ming [5 ]
Stevens, Valerie [6 ]
Fuqua, Brie K. [1 ]
Andersen, Henriette S. [6 ]
Naylor, Claire E. [7 ]
Evans, Robert W. [8 ]
Gambling, Lorraine [6 ]
Danzeisen, Ruth [6 ,9 ]
Bacouri-Haidar, Mhenia [10 ]
Usta, Julnar [11 ]
Vulpe, Chris D. [1 ]
McArdle, Harry J. [6 ]
机构
[1] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA
[2] Nanjing Univ, Sch Med, Nanjing 210008, Jiangsu Prov, Peoples R China
[3] Amer Univ Sci & Technol, Dept Lab Sci & Technol, Ashrafieh 1100, Lebanon
[4] Visiongain Ltd, London EC1V 2QY, England
[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[6] Univ Aberdeen, Rowett Inst Nutr & Hlth, Bucksburn AB21 9SB, Aberdeen, Scotland
[7] Birkbeck Coll, Dept Crystallog, London WC1E 7HX, England
[8] Brunel Univ, Div Biosci, Ctr Infect Immun & Dis Mech, Sch Hlth Sci & Social Care, Uxbridge UB8 3PH, Middx, England
[9] Int Copper Assoc Inc, New York, NY 10016 USA
[10] Lebanese Univ, Dept Biol, Fac Sci, Hadath 1500, Lebanon
[11] Amer Univ Beirut, Dept Biochem, Sch Med, Beirut 1103, Lebanon
关键词
INTESTINAL IRON TRANSPORT; DIETARY COPPER DEFICIENCY; CERULOPLASMIN HOMOLOG; CRYSTAL-STRUCTURE; HEPHAESTIN; PROTEIN; GENE; EXPRESSION; OXIDASE; DISRUPTION;
D O I
10.3945/jn.109.117531
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 [营养与食品卫生学];
摘要
We previously detected a membrane-bound, copper-containing oxidase that may be involved in iron efflux in BeWo cells, a human placental cell line. We have now identified a gene encoding a predicted multicopper ferroxidase (MCF) with a putative C-terminal membrane-spanning sequence and high sequence identity to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate MCF. Molecular modeling revealed conservation of all type I, II, and III copper-binding sites as well as a putative iron-binding site. Protein expression was observed in multiple diverse mouse tissues, including placenta and mammary gland, and the expression pattern was distinct from that of Cp and Heph. The protein possessed ferroxidase activity, and protein levels decreased in cellular copper deficiency. Knockdown with small interfering RNA in BeWo cells indicates that this gene represents the previously detected oxidase. We propose calling this new member of the MCF family "zyklopen." J. Nutr. 140: 1728-1735, 2010.
引用
收藏
页码:1728 / 1735
页数:8
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