TRPC1 Deletion Causes Striatal Neuronal Cell Apoptosis and Proteomic Alterations in Mice.
TRPC1 Deletion Causes Striatal Neuronal Cell Apoptosis and Proteomic Alterations in Mice.
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TRPC1 缺失导致小鼠纹状体神经元细胞凋亡和蛋白质组改变
DOI：
10.3389/fnagi.2018.00072
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发表时间：
2018
影响因子：
4.8
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Wang D;Yu H;Xu B;Xu H;Zhang Z;Ren X;Yuan J;Liu J;Guo Y;Spencer PS;Yang X
瞬时受体电位通道1（TRPC 1）在整个神经系统中广泛表达，但其生物学作用尚不清楚。在这项研究中，我们发现TRPC 1缺失导致纹状体神经元丢失，并显著增加纹状体中的TUNEL阳性和8-羟基-2 ′-脱氧鸟苷（8-OHdG）染色。通过二维荧光差异凝胶电泳（2D-DIGE）结合质谱（MS）进行的蛋白质组学分析显示，与野生型（WT）小鼠相比，TRPC 1敲除（TRPC 1 −/−）小鼠的分层中共有51个差异表达蛋白（26个增加，25个减少）。生物信息学分析表明，这些表达异常的蛋白包括：氧化应激相关蛋白、突触蛋白、内质网应激相关蛋白和凋亡相关蛋白。STRING分析表明，这些差异蛋白具有良好的相互作用网络。基于蛋白质组学数据，我们通过Western-blot分析揭示，TRPC 1缺失导致ER应激，表现为GRP 78和PERK激活相关信号通路的失调，以及氧化应激的升高，表现为增加的8-OHdG染色，增加的NADH脱氢酶（泛醌）黄素蛋白2（NDUV 2）和减少的蛋白脱糖酶（DJ-1），两种氧化应激相关蛋白。此外，我们还证明了TRPC 1缺失导致纹状体细胞凋亡显著增加，同时减少14-3- 3 Z和动力蛋白-1（D2多巴胺（DA）受体结合），两种凋亡相关蛋白。综上所述，我们得出结论，TRPC 1缺失可能通过干扰多种生物过程（即，ER应激、氧化应激和糖尿病相关信号传导）。这些数据表明TRPC 1可能是调节纹状体细胞存活和死亡的关键参与者。
Transient receptor potential channel 1 (TRPC1) is widely expressed throughout the nervous system, while its biological role remains unclear. In this study, we showed that TRPC1 deletion caused striatal neuronal loss and significantly increased TUNEL-positive and 8-hydroxy-2′-deoxyguanosine (8-OHdG) staining in the striatum. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) revealed a total of 51 differentially expressed proteins (26 increased and 25 decreased) in the stratum of TRPC1 knockout (TRPC1−/−) mice compared to that of wild type (WT) mice. Bioinformatics analysis showed these dysregulated proteins included: oxidative stress-related proteins, synaptic proteins, endoplasmic reticulum (ER) stress-related proteins and apoptosis-related proteins. STRING analysis showed these differential proteins have a well-established interaction network. Based on the proteomic data, we revealed by Western-blot analysis that TRPC1 deletion caused ER stress as evidenced by the dysregulation of GRP78 and PERK activation-related signaling pathway, and elevated oxidative stress as suggested by increased 8-OHdG staining, increased NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUV2) and decreased protein deglycase (DJ-1), two oxidative stress-related proteins. In addition, we also demonstrated that TRPC1 deletion led to significantly increased apoptosis in striatum with concurrent decrease in both 14–3–3Z and dynamin-1 (D2 dopamine (DA) receptor binding), two apoptosis-related proteins. Taken together, we concluded that TRPC1 deletion might cause striatal neuronal apoptosis by disturbing multiple biological processes (i.e., ER stress, oxidative stress and apoptosis-related signaling). These data suggest that TRPC1 may be a key player in the regulation of striatal cellular survival and death.
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影响因子：
21.3
作者：
Tabas, Ira;Ron, David
通讯作者：
Ron, David
TRPC1 在甲状腺激素依赖性多巴胺能神经元发育中的关键作用
DOI：
10.1016/j.bbamcr.2017.07.019
发表时间：
2017-10-01
影响因子：
5.1
作者：
Chen, Chunhai;Ma, Qinglong;Zhou, Zhou
通讯作者：
Zhou, Zhou
影响因子：
15.9
作者：
Selvaraj, Senthil;Sun, Yuyang;Singh, Brij B.
通讯作者：
Singh, Brij B.
TRPC1-STIM1 复合物对 L 型 Ca(2 ) 通道的抑制对于保护多巴胺能神经元至关重要。
影响因子：
5.3
作者：
Sun, Yuyang;Zhang, Haopeng;Singh, Xbrij B.
通讯作者：
Singh, Xbrij B.
哺乳动物转录因子 ATF6 以跨膜蛋白的形式合成，并在内质网应激时通过蛋白水解激活
影响因子：
3.3
作者：
Haze, K;Yoshida, H;Mori, K
通讯作者：
Mori, K