Transcriptomic profile analysis of brain inferior colliculus following acute hydrogen sulfide exposure.
Transcriptomic profile analysis of brain inferior colliculus following acute hydrogen sulfide exposure.
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DOI：
10.1016/j.tox.2019.152345
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发表时间：
2020-01-30
期刊：
影响因子：
4.5
通讯作者：
Rumbeiha WK
中科院分区：
文献类型：
--
作者：
Kim DS;Anantharam P;Padhi P;Thedens DR;Li G;Gilbreath E;Rumbeiha WK
硫化氢（H2S）是一种天然存在于环境中的气体分子，是一种工业副产品，已知在急性高剂量暴露后会导致急性死亡并诱发长期神经系统疾病。目前，还没有药物被批准用于治疗急性h2s诱导的神经毒性和/或神经系统后遗症。由于对硫化氢诱导的神经毒性的发病机制缺乏深入的了解，阻碍了针对硫化氢诱导的神经病理学的适当治疗药物的开发。通过RNA测序分析，阐明h2s诱导神经变性的细胞和分子机制，并确定h2s诱导神经毒性的关键分子元件和途径。C57BL/6J小鼠全身吸入700 ppm H2S暴露1天、连续2天或连续4天。磁共振成像（MRI）扫描分析显示H2S暴露导致下丘（IC）和丘脑（TH）病变。RNA测序分析显示，暴露1次、2次和4次的小鼠分别有283、193和296个差异表达基因（DEG） （q值< 0.05,fold-change > 1.5）。硫化氢暴露可调节IC中的多种生物通路，包括未折叠蛋白反应、神经递质、氧化应激、缺氧、钙信号和炎症反应。硫化氢暴露可激活PI3K/Akt和MAPK信号通路。研究表明，促炎细胞因子是H2S暴露后调节信号通路的潜在启动物。此外，小胶质细胞释放IL-18，星形胶质细胞释放IL-1β和IL-18响应H2S。这些转录组学分析数据揭示了h2s诱导神经毒性的复杂信号通路，并可能提供重要的相关机制见解。
Hydrogen sulfide (H2S) is a gaseous molecule found naturally in the environment, and as an industrial byproduct, and is known to cause acute death and induces long-term neurological disorders following acute high dose exposures. Currently, there is no drug approved for treatment of acute H2S-induced neurotoxicity and/or neurological sequelae. Lack of a deep understanding of pathogenesis of H2S-induced neurotoxicity has delayed the development of appropriate therapeutic drugs that target H2S-induced neuropathology. RNA sequencing analysis was performed to elucidate the cellular and molecular mechanisms of H2S-induced neurodegeneration, and to identify key molecular elements and pathways that contribute to H2S-induced neurotoxicity. C57BL/6J mice were exposed by whole body inhalation to 700 ppm of H2S for either one day, two consecutive days or 4 consecutive days. Magnetic resonance imaging (MRI) scan analyses showed H2S exposure induced lesions in the inferior colliculus (IC) and thalamus (TH). This mechanistic study focused on the IC. RNA Sequencing analysis revealed that mice exposed once, twice, or 4 times had 283, 193 and 296 differentially expressed genes (DEG), respectively (q-value < 0.05, fold-change > 1.5). Hydrogen sulfide exposure modulated multiple biological pathways including unfolded protein response, neurotransmitters, oxidative stress, hypoxia, calcium signaling, and inflammatory response in the IC. Hydrogen sulfide exposure activated PI3K/Akt and MAPK signaling pathways. Pro-inflammatory cytokines were shown to be potential initiators of the modulated signaling pathways following H2S exposure. Furthermore, microglia were shown to release IL-18 and astrocytes released both IL-1β and IL-18 in response to H2S. This transcriptomic analysis data revealed complex signaling pathways involved in H2S-induced neurotoxicity and may provide important associated mechanistic insights.
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影响因子：
3.4
作者：
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