Ribosomal S6 kinase regulates ischemia-induced progenitor cell proliferation in the adult mouse hippocampus.
Ribosomal S6 kinase regulates ischemia-induced progenitor cell proliferation in the adult mouse hippocampus.
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DOI：
10.1016/j.expneurol.2013.11.022
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发表时间：
2014-03
影响因子：
5.3
通讯作者：
Obrietan, Karl
中科院分区：
文献类型：
--
作者：
Karelina, Kate;Alzate-Correa, Diego;Obrietan, Karl
缺血诱导的祖细胞增殖是成年哺乳动物脑再生由病理生理过程引起的损伤组织的能力的突出例子。为了更好地理解和利用细胞信号转导机制，调节缺血诱导的增殖，我们研究了p42/44丝裂原活化蛋白激酶（MAPK）级联效应核糖体S6激酶（RSK）在这一过程中的作用。在这里，使用内皮素-1缺血模型在野生型小鼠，我们表明，RSK的激活形式表达在海马脑缺血后的颗粒下区（SGZ）的祖细胞。此外，RSK抑制显著降低缺血诱导的SGZ祖细胞增殖。使用神经球测定，我们还表明，SGZ和脑室下区（SVZ）衍生的成体神经干细胞（NSC）表现出显着减少RSK和MAPK抑制剂的存在下增殖。总之，这些数据揭示了RSK作为缺血诱导的祖细胞增殖的调节剂，因此，表明通过特异性靶向调节SGZ祖细胞群中的RSK可以获得潜在的治疗价值。
Ischemia-induced progenitor cell proliferation is a prominent example of the adult mammalian brain’s ability to regenerate injured tissue resulting from pathophysiological processes. In order to better understand and exploit the cell signaling mechanisms that regulate ischemia-induced proliferation, we examined the role of the p42/44 mitogen-activated protein kinase (MAPK) cascade effector ribosomal S6 kinase (RSK) in this process. Here, using the endothelin-1 ischemia model in wild type mice, we show that the activated form of RSK is expressed in the progenitor cells of the subgranular zone (SGZ) after intrahippocampal cerebral ischemia. Further, RSK inhibition significantly reduces ischemia-induced SGZ progenitor cell proliferation. Using the neurosphere assay, we also show that both SGZ- and subventricular zone (SVZ)-derived adult neural stem cells (NSC) exhibit a significant reduction in proliferation in the presence of RSK and MAPK inhibitors. Taken together, these data reveal RSK as a regulator of ischemia-induced progenitor cell proliferation, and as such, suggest potential therapeutic value may be gained by specifically targeting the regulation of RSK in the progenitor cell population of the SGZ.
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影响因子：
16
作者：
Eisinger-Mathason, T. S. Karin;Andrade, Josefa;Groehler, Angela L.;Clark, David E.;Muratore-Schroeder, Tara L.;Pasic, Lejla;Smith, Jeffrey A.;Shabanowitz, Jeffrey;Hunt, Donald F.;Macara, Ian G.;Lannigan, Deborah A.
通讯作者：
Lannigan, Deborah A.
影响因子：
3.4
作者：
Hawes, Jessica J.;Narasimhaiah, Roopashree;Picciotto, Marina R.
通讯作者：
Picciotto, Marina R.
影响因子：
2.9
作者：
Gu, ZL;Jiang, Q;Zhang, CY
通讯作者：
Zhang, CY
DOI：
10.1016/j.bbrc.2008.03.060
发表时间：
2008-05-23
影响因子：
3.1
作者：
Fujita, Yuko;Hiroyama, Masami;Tanoue, Akito
通讯作者：
Tanoue, Akito
影响因子：
4.1
作者：
Frödin, M;Gammeltoft, S
通讯作者：
Gammeltoft, S