Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia.
Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia.
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DOI：
10.1038/srep06343
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发表时间：
2014-09-11
影响因子：
4.6
通讯作者：
Fujiwara R
中科院分区：
文献类型：
--
作者：
Aoshima N;Fujie Y;Itoh T;Tukey RH;Fujiwara R
热量摄入不足或饥饿被认为是新生儿黄疸的原因，这可能进一步导致永久性脑损伤，核黄疸。本研究通过实验研究了额外的葡萄糖治疗是否会诱导胆红素代谢酶-UDP-葡萄糖醛酸转移酶（UGT）1A 1-来预防新生儿高胆红素血症的发生。新生人源化UGT 1（hUGT 1）小鼠在生理上发展黄疸。在这项研究中，UGT 1A 1的表达水平，测定了肝脏和小肠的新生hUGT 1小鼠口服葡萄糖治疗。在hUGT 1小鼠中，葡萄糖诱导小肠中的UGT 1A 1，而不影响肝脏中UGT 1A 1的表达。当细胞在葡萄糖存在下培养时，UGT 1A 1也在人肠Caco-2细胞中诱导。荧光素酶分析表明，不仅UGT 1A 1启动子的近端区域（-1300/-7），而且远端区域（-6500/-4050）负责在肠细胞中诱导UGT 1A 1。充足的热量摄入将导致UGT 1A 1在小肠中充分表达，从而降低血清胆红素水平。用葡萄糖溶液补充治疗新生儿可以是治疗新生儿黄疸的方便有效的方法，同时允许连续母乳喂养。
Inadequate calorie intake or starvation has been suggested as a cause of neonatal jaundice, which can further cause permanent brain damage, kernicterus. This study experimentally investigated whether additional glucose treatments induce the bilirubin-metabolizing enzyme – UDP-glucuronosyltransferase (UGT) 1A1 – to prevent the onset of neonatal hyperbilirubinemia. Neonatal humanized UGT1 (hUGT1) mice physiologically develop jaundice. In this study, UGT1A1 expression levels were determined in the liver and small intestine of neonatal hUGT1 mice that were orally treated with glucose. In the hUGT1 mice, glucose induced UGT1A1 in the small intestine, while it did not affect the expression of UGT1A1 in the liver. UGT1A1 was also induced in the human intestinal Caco-2 cells when the cells were cultured in the presence of glucose. Luciferase assays demonstrated that not only the proximal region (-1300/-7) of the UGT1A1 promoter, but also distal region (-6500/-4050) were responsible for the induction of UGT1A1 in the intestinal cells. Adequate calorie intake would lead to the sufficient expression of UGT1A1 in the small intestine to reduce serum bilirubin levels. Supplemental treatment of newborns with glucose solution can be a convenient and efficient method to treat neonatal jaundice while allowing continuous breastfeeding.
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影响因子：
5.1
作者：
Maruo, Yoshihiro;Morioka, Yoriko;Fujito, Hiroshi;Nakahara, Sayuri;Yanagi, Takahide;Matsui, Katsuyuki;Mori, Asami;Sato, Hiroshi;Tukey, Robert H.;Takeuchi, Yoshihiro
通讯作者：
Takeuchi, Yoshihiro
影响因子：
5.1
作者：
GARTNER, LM;LEE, KS;ZARAFU, I
通讯作者：
ZARAFU, I
影响因子：
2.3
作者：
Kumar, Praveen;Murki, Srinivas;Singh, S. N.
通讯作者：
Singh, S. N.
影响因子：
3
作者：
MEDLEY, MM;HOOKER, RL;JAFFE, BM
通讯作者：
JAFFE, BM
影响因子：
3.9
作者：
Senekeo-Effenberger, Kathy;Chen, Shujuan;Tukey, Robert H.
通讯作者：
Tukey, Robert H.