Endothelial cells regulate p53-dependent apoptosis of neural progenitors after irradiation.
Endothelial cells regulate p53-dependent apoptosis of neural progenitors after irradiation.
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DOI：
10.1038/cddis.2012.59
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发表时间：
2012-06-21
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
内皮细胞是神经源性微生态位的重要组成部分，可以调节神经祖细胞（NPC）的自我更新和分化。它们是否在应激或损伤后决定NPC的凋亡命运中起作用尚不清楚。已知NPC在电离辐射后经历p53依赖性凋亡，而辐射后的内皮细胞凋亡依赖于膜酸性鞘磷脂酶（ASMase），并且在鞘磷脂磷酸二酯酶1（smpd 1）-（编码ASMase的基因）缺陷型小鼠中被废除。在这里，我们发现，p53依赖性凋亡的NPC在体内照射后受到抑制smpd 1缺陷小鼠。然而，从野生型（+/+）或smpd 1基因敲除（−/−）小鼠培养的NPC在凋亡放射敏感性方面没有差异。与移植到smpd 1 +/+小鼠中的NPC相比，移植到smpd 1 −/−小鼠海马中的NPC在辐射后免受凋亡。静脉注射碱性成纤维细胞生长因子，它不会穿过血脑屏障，已知保护内皮细胞免受辐射后的凋亡也减弱了NPC的凋亡反应。这些研究结果提供了证据，内皮细胞可能会调节p53依赖性细胞凋亡的NPC基因毒性应激后，并增加了支持的重要作用，内皮细胞在调节细胞凋亡的NPC损伤后或疾病。
Endothelial cells represent an important component of the neurogenic niche and may regulate self-renewal and differentiation of neural progenitor cells (NPCs). Whether they have a role in determining the apoptotic fate of NPCs after stress or injury is unclear. NPCs are known to undergo p53-dependent apoptosis after ionizing radiation, whereas endothelial cell apoptosis after irradiation is dependent on membrane acid sphingomyelinase (ASMase) and is abrogated in sphingomyelin phosphodiesterase 1 (smpd1)- (gene that encodes ASMase) deficient mice. Here we found that p53-dependent apoptosis of NPCs in vivo after irradiation was inhibited in smpd1-deficient mice. NPCs cultured from mice, wild type (+/+) or knockout (−/−), of the smpd1 gene, however, demonstrated no difference in apoptosis radiosensitivity. NPCs transplanted into the hippocampus of smpd1−/− mice were protected against apoptosis after irradiation compared with those transplanted into smpd1+/+ mice. Intravenous administration of basic fibroblast growth factor, which does not cross the blood–brain barrier, known to protect endothelial cells against apoptosis after irradiation also attenuated the apoptotic response of NPCs. These findings provide evidence that endothelial cells may regulate p53-dependent apoptosis of NPCs after genotoxic stress and add support to an important role of endothelial cells in regulating apoptosis of NPCs after injury or in disease.
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影响因子：
23.9
作者：
Shen Q;Wang Y;Kokovay E;Lin G;Chuang SM;Goderie SK;Roysam B;Temple S
通讯作者：
Temple S
影响因子：
1.7
作者：
Limoli, C. L.;Giedzinski, E.;Fike, J. R.
通讯作者：
Fike, J. R.
影响因子：
3.4
作者：
Mahmoud-Ahmed, AS;Atkinson, S;Wong, CS
通讯作者：
Wong, CS
DOI：
10.1097/nen.0b013e3181d1afe4
发表时间：
2010-03-01
影响因子：
3.2
作者：
Wu, Kai-Liang;Li, Yu-Qing;Wong, C. Shun
通讯作者：
Wong, C. Shun
影响因子：
12.4
作者：
Hahn, P;Lindsten, T;Dunaief, JL
通讯作者：
Dunaief, JL