Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney.
Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney.
复制标题
火铁黄蛋白和铜蓝蛋白促进小鼠肾脏中的铁代谢
DOI：
10.1038/srep39470
复制
发表时间：
2016-12-19
影响因子：
4.6
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Jiang B;Liu G;Zheng J;Chen M;Maimaitiming Z;Chen M;Liu S;Jiang R;Fuqua BK;Dunaief JL;Vulpe CD;Anderson GJ;Wang H;Chen H
多铜铁氧化物酶(MCFs)在细胞铁稳态中起着重要作用。然而，MCFs在肾脏代谢中的作用仍不清楚。我们用Hephaestin(Heph)和铜蓝蛋白(CP)单基因或双基因(Heph/CP)基因敲除(KO)小鼠来研究MCFs在肾脏中的作用。检测肾组织铁水平及铁代谢相关基因的表达。HEPH/CpKO组小鼠肾皮质和髓质中非血红素铁含量均显著增加。Perls‘s普鲁士蓝染色显示，在Heph/CpKO小鼠肾小管上皮细胞顶端有铁聚集。在Heph/CpKO小鼠的肾髓质和皮质中，铁蛋白的表达也显著增加。HEPH/CpKO小鼠肾髓质中DMT1和TfR1蛋白表达均显著降低，而肾皮质中DMT1蛋白表达显著增加。在双基因敲除小鼠中观察到蛋白尿和尿铁总量显著增加，这与结构完整性受损有关。这些结果表明，HEPH和CP基因的KO均导致肾脏铁沉积和毒性，MCFs对铁过量所致的肾脏损伤具有保护作用。
Multicopper ferroxidases (MCFs) play an important role in cellular iron homeostasis. However, the role of MCFs in renal metabolism remains unclear. We used Hephaestin (Heph) and Ceruloplasmin (Cp) single or double (Heph/Cp) knockout (KO) mice to study the roles of MCFs in the kidney. Renal iron levels and the expression of iron metabolism genes were examined. The non-heme iron content both in the renal cortex and medulla ofHeph/CpKO mice was significantly increased. Perls’ Prussian blue staining showed iron accumulation on the apical side of renal tubular cells inHeph/CpKO mice. A significant increase in ferritin protein expression was also observed in the renal medulla and cortex ofHeph/CpKO mice. Both DMT1 and TfR1 protein expression were significantly decreased in the renal medulla ofHeph/CpKO mice, while the expression of DMT1 protein was significantly increased in the renal cortex of these animals. Significant increase in proteinuria and total urinary iron was observed in the double knockout mice, and this was associated with compromised structural integrity. These results suggest that KO of both the HEPH and CP genes leads to kidney iron deposition and toxicity, MCFs could protect kidney against a damage from iron excess.
登录
查看更多内容
DOI：
10.1152/ajprenal.00359.2005
发表时间：
2006-06-01
影响因子：
4.2
作者：
Abouhamed, M;Gburek, J;Smith, CP
通讯作者：
Smith, CP
影响因子：
4.8
作者：
Patel, BN;David, S
通讯作者：
David, S
影响因子：
20.3
作者：
Chen, HJ;Su, T;Vulpe, CD
通讯作者：
Vulpe, CD
影响因子：
4.5
作者：
Galleano, M;Puntarulo, S
通讯作者：
Puntarulo, S
影响因子：
2.6
作者：
Kato, Junji;Kobune, Masayoshi;Niitsu, Yoshiro
通讯作者：
Niitsu, Yoshiro