Broad spectrum proteomics analysis of the inferior colliculus following acute hydrogen sulfide exposure.
Broad spectrum proteomics analysis of the inferior colliculus following acute hydrogen sulfide exposure.
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DOI：
10.1016/j.taap.2018.06.001
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发表时间：
2018-09-15
影响因子：
3.8
通讯作者：
Rumbeiha WK
中科院分区：
文献类型：
--
作者：
Kim DS;Anantharam P;Hoffmann A;Meade ML;Grobe N;Gearhart JM;Whitley EM;Mahama B;Rumbeiha WK
急性暴露于高浓度的 H2S 会导致严重的脑损伤和长期的神经系统疾病，但所涉及的机制尚不清楚。为了更好地了解急性 H2S 诱导的神经变性的细胞和分子机制，我们使用广谱蛋白质组分析方法来识别参与急性 H2S 诱导的神经毒性和神经变性发病机制的关键分子和分子途径。小鼠急性吸入高达 750 ppm 的 H2S。 H2S 会导致行为缺陷和严重损伤，包括下丘 (IC) 出血。对 IC 进行显微解剖以进行蛋白质组分析。基于串联质量标签 (TMT) 液相色谱质谱 (LC-MS/MS) 的定量蛋白质组学用于蛋白质鉴定和定量。 LC-MS/MS 在 H2S 暴露后 2 小时、第 2 天和第 4 天分别鉴定出 598、562 和 546 个蛋白质组变化。其中，77 个蛋白质组变化在 3 个时间点中的任何一个时间点均具有统计显着性。质谱数据经过Perseus 1.5.5.3统计分析，以及基因本体热图聚类。验证了几个关键分子的表达，以确认 H2S 依赖性蛋白质组学变化。使用 Panther 引擎对 Webgestalt 通路过度表达富集分析显示，H2S 暴露破坏了多种生物过程，包括代谢型谷氨酸受体组 1 以及趋化因子和细胞因子信号通路介导的炎症等。进一步的分析表明，能量代谢、血脑屏障的完整性、缺氧和氧化应激信号通路也参与其中。总的来说，这些广谱蛋白质组学数据为后续研究提供了重要线索，以进一步阐明 H2S 诱导的神经毒性机制。
Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H2S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to 750 ppm of H2S. H2S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H2S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H2S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H2S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H2S-induced neurotoxicity.
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影响因子：
3.4
作者：
Kim, Dong-Suk;Jin, Huajun;Anantharam, Vellareddy;Gordon, Richard;Kanthasamy, Arthi;Kanthasamy, Anumantha G.
通讯作者：
Kanthasamy, Anumantha G.
影响因子：
5.2
作者：
Anantharam P;Whitley EM;Mahama B;Kim DS;Imerman PM;Shao D;Langley MR;Kanthasamy A;Rumbeiha WK
通讯作者：
Rumbeiha WK
影响因子：
5.3
作者：
Hou, ST;Jiang, SX;Kappler, J
通讯作者：
Kappler, J
影响因子：
1.6
作者：
Doujaiji, Bassam;Al-Tawfiq, Jaffar A.
通讯作者：
Al-Tawfiq, Jaffar A.
影响因子：
4.8
作者：
Dalgard CL;Cole JT;Kean WS;Lucky JJ;Sukumar G;McMullen DC;Pollard HB;Watson WD
通讯作者：
Watson WD