Pre-B-cell colony-enhancing factor protects against apoptotic neuronal death and mitochondrial damage in ischemia.
Pre-B-cell colony-enhancing factor protects against apoptotic neuronal death and mitochondrial damage in ischemia.
复制标题
前 B 细胞集落增强因子可防止缺血时神经元凋亡和线粒体损伤。
DOI：
10.1038/srep32416
复制
发表时间：
2016-08-31
影响因子：
4.6
通讯作者：
Ding S
中科院分区：
文献类型：
--
作者：
Wang X;Li H;Ding S
我们先前证明了B细胞增强因子（PBEF），也称为烟酰胺磷酸贝糖基转移酶（NAMPT），哺乳动物NAD+生物合成途径中的速率限制酶扮演脑和神经元保护在缺血性Stroke中的作用。在这项研究中，我们进一步研究了其在原发性培养小鼠皮质神经元中缺血后其神经保护作用的机制。使用凋亡细胞死亡测定，荧光成像，分子生物学，线粒体生物发生测量和蛋白质印迹分析，我们的结果表明，神经元中PBEF的过表达可以显着促进神经元的生存，减少对核酸盐和核的诱导因子（AIF）的旋转codifation codipation codibient coctimin coctimin coctimins indibimInibing insibibIn insibibim insibibim insimibim insibibIn的易位。兴奋性毒性。我们进一步发现，PBEF的过表达可以抑制谷氨酸诱导的线粒体片段化，线粒体DNA（mtDNA）含量的损失以及PGC-1和NRF-1表达的还原。此外，PBEF的这些有益作用取决于其NAD+合成的酶促活性。总而言之，我们的研究表明，PBEF通过抑制caspase依赖性和独立的凋亡信号通路并抑制线粒体损伤和功能障碍来缓解缺血诱导的神经元死亡。我们的研究提供了对PBEF神经保护作用的基础机制的新见解，并有助于确定缺血性中风治疗的潜在靶标。
We previously demonstrated that Pre-B-cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis pathway, plays a brain and neuronal protective role in ischemic stroke. In this study, we further investigated the mechanism of its neuroprotective effect after ischemia in the primary cultured mouse cortical neurons. Using apoptotic cell death assay, fluorescent imaging, molecular biology, mitochondrial biogenesis measurements and Western blotting analysis, our results show that the overexpression of PBEF in neurons can significantly promote neuronal survival, reduce the translocation of apoptosis inducing factor (AIF) from mitochondria to nuclei and inhibit the activation of capase-3 after glutamate-induced excitotoxicity. We further found that the overexpression of PBEF can suppress glutamate-induced mitochondrial fragmentation, the loss of mitochondrial DNA (mtDNA) content and the reduction of PGC-1 and NRF-1 expressions. Furthermore, these beneficial effects by PBEF are dependent on its enzymatic activity of NAD+ synthesis. In summary, our study demonstrated that PBEF ameliorates ischemia-induced neuronal death through inhibiting caspase-dependent and independent apoptotic signaling pathways and suppressing mitochondrial damage and dysfunction. Our study provides novel insights into the mechanisms underlying the neuroprotective effect of PBEF, and helps to identify potential targets for ischemic stroke therapy.
登录
查看更多内容
影响因子：
5.3
作者：
Lim SY;Davidson SM;Paramanathan AJ;Smith CC;Yellon DM;Hausenloy DJ
通讯作者：
Hausenloy DJ
影响因子：
2.5
作者：
Revollo, Javier R.;Grimm, Andrew A.;Imai, Shin-ichiro
通讯作者：
Imai, Shin-ichiro
影响因子：
4
作者：
Li, Hailong;Wang, Xiaowan;Ding, Shinghua
通讯作者：
Ding, Shinghua
影响因子：
3.1
作者：
Erfani, Sohaila;Khaksari, Mehdi;Nikbakht, Farnaz
通讯作者：
Nikbakht, Farnaz
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC