Evaluation of copper metabolism in neonatal rats by speciation analysis using liquid chromatography hyphenated to ICP mass spectrometry
Evaluation of copper metabolism in neonatal rats by speciation analysis using liquid chromatography hyphenated to ICP mass spectrometry
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DOI：
10.1039/c9mt00158a
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发表时间：
2019-10-01
期刊：
影响因子：
3.4
通讯作者：
Ogra, Yasumitsu
中科院分区：
文献类型：
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作者：
Tanaka, Yu-ki;Ogra, Yasumitsu
已知围产期铜在多个器官中高度积累，提示铜在发育过程中代谢发生变化，但其确切机制尚不清楚。为了阐明铜在新生大鼠器官中积累的机制，我们采用高效液相色谱-电感耦合等离子体质谱联用技术进行了形态分析。新生大鼠出生后即刻肝脏中的铜浓度比幼年大鼠肝脏中的铜浓度高10倍。虽然铜中的铜、锌超氧化物歧化酶(SOD)活性降低，但铜中的大部分铜与金属硫蛋白结合。与肝脏铜蓄积相反，新生大鼠血清铜浓度低是由于铜结合铜蓝蛋白的量减少所致。抗氧化蛋白1(Atox1)是一种将铜转移到ATP7B的铜伴侣蛋白，出生后两周仍保持低水平表达。这些结果表明，新生大鼠肝脏中铜的积累是由于Atox1的低表达所致，这种积累有助于在呼吸开始后将铜分配到含铜的抗氧化酶(如SOD和Atox1)中。
It is known that copper (Cu) is highly accumulated in several organs in the perinatal period, suggesting changes in Cu metabolism with development, although the precise mechanisms are still unclear. To elucidate the mechanisms underlying Cu accumulation in the organs of neonatal rats, we performed speciation analysis using high-performance liquid chromatography hyphenated to inductively coupled plasma mass spectrometry. In the neonatal rat liver immediately after birth, the Cu concentration was elevated 10-fold compared to that in the juvenile rat liver. Most of the accumulated Cu was bound to metallothionein, although Cu in Cu, zinc-superoxide dismutase (SOD) was reduced. Contrary to the hepatic Cu accumulation, the serum Cu concentrations in the neonatal rats were low due to the decreased amount of Cu bound to ceruloplasmin. The mRNA expression of antioxidant protein 1 (Atox1), a Cu chaperone that transports Cu to Atp7b, remained low up to two weeks after birth. These results suggest that Cu accumulation in the neonatal rat liver is caused by the low expression of Atox1, and the accumulation is useful to distribute Cu to Cu-containing anti-oxidative enzymes (e.g., SOD and Atox1) after respiration starts.