Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke
文献类型：期刊论文
| 作者 | Liu, Yifei4; Zhang, Yun3; Sun, Meng3; Dong, Huiqing3; Hu, Xinyuan3; Shen, Tianyi2,4; Zhou, Liqin2,4; Zhang, Lei2,4; Wang, Ting2,4; Gao, Zhaobing2,4 |
| 刊名 | GLIA
 |
| 出版日期 | 2025-07-28 |
| 页码 | 17 |
| 关键词 | apoptosis astrocyte ischemic stroke PAC channel |
| ISSN号 | 0894-1491 |
| DOI | 10.1002/glia.70073 |
| 通讯作者 | Chang, Yi(chani_1213@163.com) ; Feng, Jing(fengjing@simm.ac.cn) |
| 英文摘要 | Astrocyte is critically involved in the central nervous system homeostasis and initiates tissue pathology in response to insults to the central nervous system. However, whether and how astrocytes sense micro-environmental changes, such as ischemic stroke-associated acidification, remains largely unknown. Here we show that the proton-activated chloride (PAC) channel is widely expressed in glial cells in the brain and functionally mediates acid-induced chloride influx. Moreover, conditional knockout of the PAC channel in astrocytes, but not in microglia, reduced infarct volume in a mouse model of ischemic stroke induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Rather than the classic role of chloride channels in cell volume dysregulation-related cell death, activation of the PAC channel contributes to cell apoptosis via the Akt/Bax/Caspase 3 pathway in astrocytes and promotes inflammatory mediator release from astrocytes in response to pH oscillation and oxidative stress. Collectively, our results uncover a role of the PAC channel in astrocyte acidosis, providing a potential therapeutic target for neuroprotection in ischemic stroke. |
| WOS关键词 | INDUCED CELL-DEATH ; REACTIVE ASTROCYTES ; ANION CHANNELS ; CHLORIDE ; MECHANISMS ; GLUTAMATE ; BRAIN ; INVOLVEMENT ; MODULATION ; ACTIVATION |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China[32241003] ; National Natural Science Foundation of China[82171214] ; National Natural Science Foundation of China[U24A20783] ; National Natural Science Foundation of China[82471233] ; Shanghai Municipal Natural Science Foundation[23ZR1474500] ; National Key Research and Development Program of China[2024YFC3505305] ; State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai ; [XDB1060000] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:001538192200001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321135]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chang, Yi; Feng, Jing |
| 作者单位 | 1.Tongji Univ, Yangpu Hosp, Sch Med, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yifei,Zhang, Yun,Sun, Meng,et al. Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke[J]. GLIA,2025:17. |
| APA | Liu, Yifei.,Zhang, Yun.,Sun, Meng.,Dong, Huiqing.,Hu, Xinyuan.,...&Feng, Jing.(2025).Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke.GLIA,17. |
| MLA | Liu, Yifei,et al."Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke".GLIA (2025):17. |
入库方式： OAI收割
来源：上海药物研究所
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