TY - JOUR
T1 - Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status
T2 - A study of the effects of zinc deficiency during lactation
AU - Hashimoto, Ayako
AU - Nakagawa, Miki
AU - Tsujimura, Natsuki
AU - Miyazaki, Shiho
AU - Kizu, Kumiko
AU - Goto, Tomoko
AU - Komatsu, Yusuke
AU - Matsunaga, Ayu
AU - Shirakawa, Hitoshi
AU - Narita, Hiroshi
AU - Kambe, Taiho
AU - Komai, Michio
N1 - Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
KW - Alkaline phosphatase
KW - Glucose homeostasis
KW - Small intestine
KW - Zinc deficiency
KW - Zip4 processing
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U2 - 10.1152/ajpregu.00439.2015
DO - 10.1152/ajpregu.00439.2015
M3 - Article
C2 - 26702153
AN - SCOPUS:84977764706
VL - 310
SP - R459-R468
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 5
ER -