miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain.
miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain.
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DOI：
10.3390/toxics11120969
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发表时间：
2023-11-30
期刊：
影响因子：
4.6
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Sun Q;Wang H;Yang M;Xia H;Wu Y;Liu Q;Tang H
香烟含有多种化学物质，会对神经细胞造成损害。暴露于香烟烟雾（CS）会导致神经细胞的胰岛素抵抗（IR）。然而，在阿糖胞苷诱导的胰岛素信号通路和神经毒性的障碍的机制仍然不清楚。因此，我们评估，通过一系列的病理分析和行为测试，慢性暴露于CS对C57 BL/6小鼠的神经毒性作用。小鼠暴露于CS与超过200 mg/m3的总颗粒物（TPM）表现出记忆缺陷和认知障碍。小鼠脑组织石蜡切片的病理染色显示，CS暴露的小鼠，在大脑中，神经元损伤的特点是更薄的锥体细胞和颗粒细胞层和更少的神经元。此外，SH-SY 5 Y细胞暴露于香烟烟雾提取物（CSE）导致胰岛素敏感性降低，葡萄糖摄取以剂量依赖性方式减少。PI 3 K/GSK 3胰岛素信号通路与神经毒性特别相关。microRNA参与PI 3 K/GSK 3 β/p-Tau通路，我们发现香烟暴露激活miR-153- 3 p，降低PI 3 K调节亚基PIK 3R 1，并诱导Tau过度磷酸化。暴露于miR-153抑制剂或PI 3 K抑制剂缓解了CS引起的胰岛素敏感性降低。因此，我们的研究结果表明，miR-153- 3 p，通过PIK 3R 1，在大脑中引起胰岛素抵抗，并参与CS诱导的神经毒性。
Cigarettes contain various chemicals that cause damage to nerve cells. Exposure to cigarette smoke (CS) causes insulin resistance (IR) in nerve cells. However, the mechanisms for a disorder in the cigarette-induced insulin signaling pathway and in neurotoxicity remain unclear. Therefore, we evaluated, by a series of pathology analyses and behavioral tests, the neurotoxic effects of chronic exposure to CS on C57BL/6 mice. Mice exposed to CS with more than 200 mg/m3 total particulate matter (TPM) exhibited memory deficits and cognitive impairment. Pathological staining of paraffin sections of mouse brain tissue revealed that CS-exposed mice had, in the brain, neuronal damage characterized by thinner pyramidal and granular cell layers and fewer neurons. Further, the exposure of SH-SY5Y cells to cigarette smoke extract (CSE) resulted in diminished insulin sensitivity and reduced glucose uptake in a dose-dependent fashion. The PI3K/GSK3 insulin signaling pathway is particularly relevant to neurotoxicity. microRNAs are involved in the PI3K/GSK3β/p-Tau pathway, and we found that cigarette exposure activates miR-153-3p, decreases PI3K regulatory subunits PIK3R1, and induces Tau hyperphosphorylation. Exposure to an miR-153 inhibitor or to a PI3K inhibitor alleviated the reduced insulin sensitivity caused by CS. Therefore, our results indicate that miR-153-3p, via PIK3R1, causes insulin resistance in the brain, and is involved in CS-induced neurotoxicity.
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影响因子：
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