Induction of hepatic metallothionein by trivalent cerium: role of interleukin 6.
Induction of hepatic metallothionein by trivalent cerium: role of interleukin 6.
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DOI：
10.1248/bpb.28.1859
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发表时间：
2005-10
影响因子：
2
通讯作者：
Kazuo Kobayashi;Rumi Shida;T. Hasegawa;M. Satoh;Y. Seko;C. Tohyama;J. Kuroda;N. Shibata;N. Imura
中科院分区：
文献类型：
--
作者：
Kazuo Kobayashi;Rumi Shida;T. Hasegawa;M. Satoh;Y. Seko;C. Tohyama;J. Kuroda;N. Shibata;N. Imura
金属硫蛋白（MT）是一种富含巯基的小分子蛋白质，可与汞、镉、锌和铜等重金属结合并被其诱导。然而，除了铋之外，关于三价金属对MT的诱导知之甚少。在这项研究中，我们研究了诱导MT合成铈，三价镧系金属。给小鼠注射氯化铈（CeCl 3）可导致铈在肝脏中蓄积，并以剂量依赖性方式诱导MT。通过高效液相色谱/电感耦合氩等离子体质谱法（HPLC/ICP-MS）分析CeCl 3处理的小鼠肝脏可溶性部分中金属的分布概况表明，与MT-I和MT-II结合的金属是锌，但不是铈。CeCl 3的管理引起血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的活动和血清淀粉样蛋白A（SAA），一种急性时相蛋白的水平增加。在检查的炎性细胞因子中，白细胞介素6（IL-6）在CeCl 3给药后3小时血清中显示出显著增加。为了评估IL-6参与铈诱导MT，我们研究了CeCl 3在IL-6缺失小鼠中的MT诱导。在IL-6基因敲除小鼠中，肝脏MT的诱导和SAA水平的增加均被显著抑制。提示IL-6在铈诱导肝MT的过程中起重要作用。
Metallothionein (MT) is a small sulfydryl-rich protein that binds to and is inducible by heavy metals such as mercury, cadmium, zinc, and copper. However, little is known about the induction of MT by trivalent metals except for bismuth. In this study, we examined the induction of MT synthesis by cerium, a trivalent lanthanoid metal. Administration of cerium chloride (CeCl3) to mice resulted in accumulation of cerium and induction of MT in the liver in a dose-dependent manner. Distribution profiles of metals in the soluble fraction of the liver of CeCl3-treated mice analyzed by high performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) demonstrated that the metal bound to MT-I and MT-II was zinc, but not cerium. Administration of CeCl3 caused increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of serum amyloid A (SAA), an acute phase protein. Among inflammatory cytokines examined, interleukin 6 (IL-6) exhibited a marked increase in the serum at 3 h after the CeCl3 administration. In order to evaluate the involvement of IL-6 in the induction of MT by cerium, we examined MT induction by CeCl3 in IL-6 null mice. Both the induction of hepatic MT and the increases in SAA levels were markedly suppressed in IL-6 null mice. These results suggest that IL-6 plays an important role in the induction of hepatic MT by cerium.