Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway.
Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway.
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缺血性损伤诱导的 CaMKIIδ 和 CaMKIIγ 通过 NF-κB 信号通路提供神经保护
DOI：
10.1007/s12035-018-1198-2
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发表时间：
2019-03
影响因子：
5.1
通讯作者：
Wang QJ
中科院分区：
文献类型：
--
作者：
Ye J;Das S;Roy A;Wei W;Huang H;Lorenz-Guertin JM;Xu Q;Jacob TC;Wang B;Sun D;Wang QJ
长期以来，Ca2+/钙调素依赖性蛋白激酶II （CaMKII）与急性缺血/再灌注（I/R）引起的神经元损伤有关。然而，其确切作用和调控机制仍不清楚。在这里，我们研究了CaMKII家族在I/R期间神经元存活中的作用。我们的数据表明，急性缺血后，CAMK2D/CaMKIIδ和CAMK2G/CaMKIIγ在转录和蛋白水平上以时间依赖的方式选择性上调。CaMKIIδ的过表达促进了神经元的存活，而CaMKIIδ的缺失加剧了缺血性神经元的死亡。与CaMKIIδ类似，CAMKIIγ的下调导致I/R后显著的神经元死亡。我们进一步确定CaMKIIδ2是在初级神经元中选择性地被I/R诱导的亚型。CaMKIIδ的诱导部分由一对长链非编码rna (lncRNAs) C2dat1和C2dat2控制。与C2dat1类似，C2dat2通过I/R上调，并与C2dat1协同调节CaMKIIδ的表达。敲低C2dat1/2可阻断OGD/ r诱导的CaMKIIδ表达，降低神经元存活率，但不影响CaMKIIγ水平，表明C2dat1/2特异性靶向CAMK2D。在机制上，I/ r诱导的CaMKIIδ和CaMKIIγ引起IKKα/β上调，并进一步激活NF-κB信号通路，以保护神经元免受缺血性损伤。基因上，下调小鼠NF-κB p65亚基可通过阻断CaMKII/IKK/I -κB α/NF-κB信号轴活性增加I/ r诱导的神经元死亡。综上所述，CaMKIIδ和CaMKIIγ是在缺血性损伤中促进神经元存活的新型I/ r诱导基因。这些CaMKII激酶的上调导致NF-κB信号通路的激活，从而保护神经元免受缺血性损伤。本文的在线版本（10.1007/s12035-018-1198-2）包含补充资料，仅供授权用户使用。
Ca2+/calmodulin-dependent protein kinase II (CaMKII) has long been implicated in neuronal injury caused by acute ischemia/reperfusion (I/R). However, its precise role and regulatory mechanisms remain obscure. Here, we investigated the role of the CaMKII family in neuronal survival during I/R. Our data indicated that CAMK2D/CaMKIIδ and CAMK2G/CaMKIIγ were selectively upregulated in a time-dependent manner at both transcriptional and protein levels after acute ischemia. Overexpression of CaMKIIδ promoted neuronal survival, while their depletion exacerbated ischemic neuronal death. Similar to CaMKIIδ, knockdown of CAMKIIγ resulted in significant neuronal death after I/R. We further identified CaMKIIδ2 as the subtype that is selectively induced by I/R in primary neurons. The induction of CaMKIIδ was controlled in part by a pair of long non-coding RNAs (lncRNAs), C2dat1 and C2dat2. C2dat2, similar to C2dat1, was upregulated by I/R and cooperated with C2dat1 to modulate CaMKIIδ expression. Knockdown of C2dat1/2 blocked OGD/R-induced CaMKIIδ expression and decreased neuronal survival but did not affect the levels of CaMKIIγ, indicating specific targeting of CAMK2D by C2dat1/2. Mechanistically, I/R-induced CaMKIIδ and CaMKIIγ caused the upregulation of IKKα/β and further activation of the NF-κB signaling pathway to protect neurons from ischemic damage. Genetically, downregulating p65 subunit of NF-κB in mice increased I/R-induced neuronal death by blocking the activity of CaMKII/IKK/IκBα/NF-κB signaling axis. In summary, CaMKIIδ and CaMKIIγ are novel I/R-induced genes that promote neuronal survival during ischemic injury. The upregulation of these CaMKII kinases led to activation of the NF-κB signaling pathway, which protects neurons from ischemic damage. The online version of this article (10.1007/s12035-018-1198-2) contains supplementary material, which is available to authorized users.
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影响因子：
8.2
作者：
Coultrap, Steven J.;Vest, Rebekah S.;Ashpole, Nicole M.;Hudmon, Andy;Bayer, K. Ulrich
通讯作者：
Bayer, K. Ulrich
长链非编码 RNA C2dat1 调节 CaMKII delta 表达，通过 NF-kappa B 信号通路促进脑缺血后神经元存活
影响因子：
9
作者：
Xu Q;Deng F;Xing Z;Wu Z;Cen B;Xu S;Zhao Z;Nepomuceno R;Bhuiyan MI;Sun D;Wang QJ;Ji A
通讯作者：
Ji A
DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
通讯作者：
Korthuis, Ronald J.
影响因子：
64.8
作者：
Lee, Seok-Jin R.;Escobedo-Lozoya, Yasmin;Szatmari, Erzsebet M.;Yasuda, Ryohei
通讯作者：
Yasuda, Ryohei
影响因子：
3.7
作者：
Merali Z;Gao MM;Bowes T;Chen J;Evans K;Kassner A
通讯作者：
Kassner A