Endothelin-1, over-expressed in SOD1(G93A) mice, aggravates injury of NSC34-hSOD1G93A cells through complicated molecular mechanism revealed by quantitative proteomics analysis.
Endothelin-1, over-expressed in SOD1(G93A) mice, aggravates injury of NSC34-hSOD1G93A cells through complicated molecular mechanism revealed by quantitative proteomics analysis.
复制标题
DOI：
10.3389/fncel.2022.1069617
复制
发表时间：
2022
影响因子：
5.3
通讯作者：
Guo, Yansu
中科院分区：
文献类型：
--
作者：
Zhang, Yingzhen;Chen, Lin;Li, Zhongzhong;Li, Dongxiao;Wu, Yue;Guo, Yansu
内皮素-1(ET-1)是一种分泌型信号肽，参与了包括脑在内的多种组织的多种活动，但其在肌萎缩侧索硬化症(ALS)中的作用尚不清楚。本研究检测了转基因SOD-G93A(TgSOD-G93A)小鼠脊髓内ET-1、ET-A和ET-B受体的表达变化和细胞定位，结果表明，这两种ET受体主要表达在神经元上，并随着疾病的进展而减少，尤其是ET-B，而ET-1表达上调，主要定位于星形胶质细胞。然后，我们探讨了ET-1对培养的NSC34-hSOD1G93A细胞模型的可能作用机制。ET-1对运动神经元(MNS)有毒性作用，选择性ET-A受体拮抗剂BQ-123或ET-B受体拮抗剂BQ-788可拮抗ET-1对运动神经元的毒性作用，提示临床应用ET-Rs泛拮抗剂可能是治疗ALS的一种潜在策略。蛋白质组学分析表明，ET-1处理后NSC34-hSOD1G93A细胞中有110个蛋白质表达差异，其中54个蛋白质表达上调，56个蛋白质表达下调。生物信息学分析表明，差异表达蛋白主要集中在河马多物种信号通路、ABC转运蛋白、ErbB信号通路等方面。这些结果进一步揭示了ET-1在肌萎缩侧索硬化症中的潜在作用，并为保护肌萎缩侧索硬化症MNS提供了一个新的有希望的治疗靶点。
Endothelin-1 (ET-1), a secreted signaling peptide, is suggested to be involved in multiple actions in various tissues including the brain, but its role in amyotrophic lateral sclerosis (ALS) remains unknown. In this study, we detected the expression changes as well as the cellular localization of ET-1, endothelin A (ET-A) and endothelin B (ET-B) receptors in spinal cord of transgenic SOD1-G93A (TgSOD1-G93A) mice, which showed that the two ET receptors (ET-Rs) expressed mainly on neurons and decreased as the disease progressed especially ET-B, while ET-1 expression was up-regulated and primarily localized on astrocytes. We then explored the possible mechanisms underlying the effect of ET-1 on cultured NSC34-hSOD1G93A cell model. ET-1 showed toxic effect on motor neurons (MNs), which can be rescued by the selective ET-A receptor antagonist BQ-123 or ET-B receptor antagonist BQ-788, suggesting that clinically used ET-Rs pan-antagonist could be a potential strategy for ALS. Using proteomic analysis, we revealed that 110 proteins were differentially expressed in NSC34-hSOD1G93A cells after ET-1 treatment, of which 54 were up-regulated and 56 were down-regulated. Bioinformatic analysis showed that the differentially expressed proteins (DEPs) were primarily enriched in hippo signaling pathway-multiple species, ABC transporters, ErbB signaling pathway and so on. These results provide further insights on the potential roles of ET-1 in ALS and present a new promising therapeutic target to protect MNs of ALS.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-17-0042
发表时间：
2018-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Fan QW;Nicolaides TP;Weiss WA
通讯作者：
Weiss WA
C9orf72 突变肌萎缩侧索硬化症患者的基因表达谱和蛋白质-蛋白质相互作用网络。
影响因子：
3.7
作者：
Kotni MK;Zhao M;Wei DQ
通讯作者：
Wei DQ
影响因子：
2.7
作者：
Gomes, Catarina;Palma, Angelina S.;Costa, Julia
通讯作者：
Costa, Julia
影响因子：
3.7
作者：
D'Antoni, S.;Ranno, E.;Catania, M. V.
通讯作者：
Catania, M. V.
影响因子：
4.2
作者：
Haryono, Andreas;Ramadhiani, Risa;Ryanto, Gusty Rizky Teguh;Emoto, Noriaki
通讯作者：
Emoto, Noriaki