Puma, but not noxa is essential for oligodendroglial cell death
Puma, but not noxa is essential for oligodendroglial cell death
复制标题
DOI：
10.1002/glia.22552
复制
发表时间：
2013-10-01
期刊：
影响因子：
6.2
通讯作者：
Kuhlmann, Tanja
中科院分区：
文献类型：
--
作者：
Hagemeier, Karin;Luerbke, Alexander;Kuhlmann, Tanja
人类脱髓鞘疾病中少突胶质细胞死亡的机制仅部分了解。在这里，我们表明，BH 3只有蛋白质彪马，但不是Noxa，是必不可少的少突胶质细胞的毒性脱髓鞘铜螯合剂cuprizone诱导的死亡。来自Noxa或Puma缺陷型小鼠的原代少突胶质细胞表现出与野生型细胞相当的分化，但Puma缺陷型少突胶质细胞对自发性、星形孢菌素或一氧化氮诱导的细胞死亡不太敏感。此外，Puma在多发性硬化（MS）病变的少突胶质细胞中表达，并且在星形孢菌素诱导细胞死亡后，Puma mRNA水平在原代人少突胶质细胞中上调。我们的数据表明，Puma对于由不同细胞死亡刺激诱导的少突胶质细胞死亡是关键的，并且可能在MS. GLIA 2013;61：1712-1723中的少突胶质细胞死亡中起作用。
The mechanisms involved in oligodendroglial cell death in human demyelinating diseases are only partly understood. Here, we demonstrate that the BH3 only protein Puma, but not Noxa, is essential for oligodendroglial cell death in toxic demyelination induced by the copper chelator cuprizone. Primary oligodendrocytes derived from Noxa- or Puma-deficient mice showed comparable differentiation to wild-type cells, but Puma-deficient oligodendrocytes were less susceptible to spontaneous, staurosporine, or nitric oxide-induced cell death. Furthermore, Puma was expressed in oligodendrocytes in multiple sclerosis (MS) lesions and Puma mRNA levels were upregulated in primary human oligodendrocytes upon cell death induction by staurosporine. Our data demonstrate that Puma is pivotal for oligodendroglial cell death induced by different cell death stimuli and might play a role in oligodendroglial cell death in MS. GLIA 2013;61:1712-1723