Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron deregulation
Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron deregulation
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DOI：
10.1016/j.nbd.2010.04.009
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发表时间：
2010-08-01
影响因子：
6.1
通讯作者：
Arosio, Paolo
中科院分区：
文献类型：
--
作者：
Poli, Maura;Derosas, Manuela;Arosio, Paolo
泛酸激酶2 （Pantothenate kinase 2, Pank2）是一种线粒体酶，它催化辅酶a合成的第一个调节步骤，并负责一种名为pank相关神经退行性疾病（PKAN）的遗传运动障碍。其特点是大脑中铁的异常积聚，特别是在苍白球。我们在一些细胞系中通过使用特定的sirna下调Pank2来研究其对铁稳态的影响。在HeLa细胞中，这导致细胞增殖和乌头酸酶活性降低，胞质铁缺乏的迹象，但线粒体铁沉积，铁转运蛋白mRNA的诱导率为12倍。Pank2沉默也在肝癌HepG2中引起铁转运蛋白mRNA的强烈诱导，在神经母细胞瘤SH-SY5Y中引起轻微的诱导，而在胶质瘤U373细胞中没有。在所有这些细胞类型中都观察到细胞生长的减少。在某些细胞类型中，pank2介导的铁转运蛋白表达的强烈改变可能改变铁向脑的转移，并与脑铁积累有关。(C) 2010爱思唯尔公司版权所有。
Pantothenate kinase 2 (Pank2) is a mitochondrial enzyme that catalyses the first regulatory step of Coenzyme A synthesis and that is responsible for a genetic movement disorder named Pank-associated neurodegeneration (PKAN). This is characterized by abnormal iron accumulation in the brain, particularly in the globus pallidus. We downregulated Pank2 in some cell lines by using specific siRNAs to study its effect on iron homeostasis. In HeLa cells this caused a reduction of cell proliferation and of aconitase activity, signs of cytosolic iron deficiency without mitochondrial iron deposition, and a 12-fold induction of ferroportin mRNA. Pank2 silencing caused a strong induction of ferroportin mRNA also in hepatoma HepG2, a modest one in neuroblastoma SH-SY5Y and none in glioma U373 cells. A reduction of cell growth was observed in all these cell types. The strong Pank2-mediated alteration of ferroportin expression in some cell types might alter iron transfer to the brain and be connected with brain iron accumulation. (C) 2010 Elsevier Inc. All rights reserved.