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癫痫点燃和匹罗卡品模型大鼠海马的蛋白质组学分析：钙调节网络中的潜在靶点。

Proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy: potential targets in calcium regulatory network.

机构信息

Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.

Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.

出版信息

Sci Rep. 2021 Apr 15;11(1):8252. doi: 10.1038/s41598-021-87555-7.

DOI:10.1038/s41598-021-87555-7
PMID:33859251
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8050094/
Abstract

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca homeostasis. Changes in ADP-ribosyl cyclase (ADPRC), lysophosphatidic acid receptor 3 (LPAR3), calreticulin, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), synaptosomal nerve-associated protein 25 (SNAP 25) and transgelin 3 proteins were probed by Western blot analysis and validated using immunohistochemistry. Inhibition of calcium influx by 8-Bromo-cADP-Ribose (8-Br-cADPR) and 2-Aminoethyl diphenylborinate (2-APB) which act via the ADPRC and LPAR3, respectively, attenuated epileptic seizures. Considering a wide range of molecular events and effective role of calcium homeostasis in epilepsy, polypharmacy with multiple realistic targets should be further explored to reach the most effective treatments.

摘要

在此，我们通过二维电泳结合基质辅助激光解吸质谱技术对癫痫的点燃和匹罗卡品模型大鼠海马体进行了蛋白质组学分析，以期为治疗癫痫发作找到新的潜在靶点。在癫痫大鼠模型中，通过二维电泳结合基质辅助激光解吸质谱技术共鉴定出左右海马体中 144 种差异表达蛋白。基于网络分析，大多数差异表达蛋白与钙稳态有关。ADPRC、溶血磷脂酸受体 3 (LPAR3)、钙网蛋白、泛素羧基末端水解酶 L1 (UCH-L1)、突触体相关蛋白 25 (SNAP 25)和转胶蛋白 3 等蛋白的变化通过 Western blot 分析进行了探究，并通过免疫组织化学进行了验证。通过 ADPRC 和 LPAR3 分别作用的 8-Bromo-cADP-Ribose (8-Br-cADPR)和 2-Aminoethyl diphenylborinate (2-APB)抑制钙内流，可减轻癫痫发作。鉴于广泛的分子事件和钙稳态在癫痫中的有效作用，应进一步探索多药联合治疗以实现最有效的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/5fca0c7315bd/41598_2021_87555_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/b5b4fbba496b/41598_2021_87555_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/186119910104/41598_2021_87555_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/019952e6b7fe/41598_2021_87555_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/ec9f49b44b74/41598_2021_87555_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/05a8090b165e/41598_2021_87555_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/5fca0c7315bd/41598_2021_87555_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/b5b4fbba496b/41598_2021_87555_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/186119910104/41598_2021_87555_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/019952e6b7fe/41598_2021_87555_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/ec9f49b44b74/41598_2021_87555_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/05a8090b165e/41598_2021_87555_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7d/8050094/5fca0c7315bd/41598_2021_87555_Fig6_HTML.jpg

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