title: Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation.
abstract: Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely.
authors.affiliation: The Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
authors.forename: Ayako
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;
authors.forename: Miki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;
authors.forename: Natsuki
authors.initials: N
authors.lastname: Tsujimura
authors.affiliation: The Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
authors.forename: Shiho
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Department of Life and Living, Osaka Seikei College, Osaka, Japan; and.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kizu
authors.affiliation: Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;
authors.forename: Tomoko
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Komatsu
authors.affiliation: Department of Food Science, Kyoto Women's University, Kyoto, Japan.
authors.forename: Ayu
authors.initials: A
authors.lastname: Matsunaga
authors.affiliation: Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shirakawa
authors.affiliation: Department of Food Science, Kyoto Women's University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Narita
authors.affiliation: The Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; kambe1@kais.kyoto-u.ac.jp.
authors.forename: Taiho
authors.initials: T
authors.lastname: Kambe
authors.affiliation: Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;
authors.forename: Michio
authors.initials: M
authors.lastname: Komai
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism*; D003677:Deficiency Diseases / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis; D007421:Intestine, Small / Q000378:metabolism*; D007774:Lactation / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013997:Time Factors; D015854:Up-Regulation; D015032:Zinc / Q000172:deficiency*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D027682:Cation Transport Proteins; C584246:Slc39a4 protein, rat; D000469:Alkaline Phosphatase; D015032:Zinc
keywords: Zip4 processing; alkaline phosphatase; glucose homeostasis; small intestine; zinc deficiency