Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection
Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection
复制标题
DOI：
10.1016/j.lfs.2005.03.031
复制
发表时间：
2005-10-28
期刊：
影响因子：
6.1
通讯作者：
Matsuoka, M
中科院分区：
文献类型：
--
作者：
Hashimoto, Y;Suzuki, H;Matsuoka, M
Humanin（HN）抑制由各种阿尔茨海默病（AD）相关损伤诱导的神经元细胞死亡。已经提出HN结合到细胞膜上的假定受体并触发与神经保护相关的信号转导级联。最近，显示HN与百日咳毒素（PTX）敏感性G蛋白偶联甲酰肽受体样-1分子（FPRL-1）结合，减少A β（1-42）聚集和原纤维形成，并抑制A β（1 -42）对单核吞噬细胞的毒性[Ying，G.，Iribarin，P.，Zhou，Y.，（1996年），中国科学院，龚，W.，张，N.，Yu，ZX，Le，Y.，崔，Y.，王，JM，2004. Humanin是一种新发现的神经保护因子，它以G蛋白偶联甲酰肽受体样1为功能受体。Journal of Immunology 172（11），7078-7085.]。我们在这里表明，siRNA介导的FPRL-1，FPR 2的小鼠对应物的表达的破坏，并没有导致衰减的HN介导的救援的神经元细胞死亡诱导的AD相关的侮辱。我们同时提供的证据表明，HN在F11细胞中的神经保护作用是由STAT 3转录因子以及某些酪氨酸激酶介导的。总之，我们推测，FPR 2以外的受体存在，介导的HN神经保护在I II神经杂交细胞。(c)2005年爱思唯尔公司All rights reserved.
Humanin (HN) inhibits neuronal cell death induced by various Alzheimer's disease (AD)-related insults. It has been proposed that HN binds to a putative receptor on the cell membrane and triggers a signal transduction cascade linked to neuroprotection. Recently, it was shown that HN binds to pertussis toxin (PTX)-sensitive G protein-coupled formylpeptide receptor-like-1 molecule (FPRL-1), reduces A beta(1-42) aggregation and fibril formation, and suppresses the A (1-42) toxicity on monomiclear phagocytic cells [Ying, G., Iribarren, P., Zhou, Y., Gong, W., Zhang, N., Yu, ZX, Le, Y., Cui, Y., Wang, J.M., 2004. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. Journal of Immunology 172 (11), 7078-7085.]. We here show that siRNA-mediated disruption of expression of the mouse counterpart of FPRL-1, FPR2, did not result in attenuation of HN-mediated rescue of neuronal cell death induced by AD-related insults. We simultaneously provide evidence that neuroprotection by HN in F11 cells is mediated by the STAT3 transcription factor as well as by certain tyrosine kinases. Altogether, we speculate that a receptor other than FPR2 exists that mediates HN neuroprotection in I'll neurohybrid cells. (c) 2005 Elsevier Inc. All rights reserved.