一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Neurochemical Research >>article
Neurochemical Research

Neurochemical Research

IF: 3.7
Download PDF

Piezo1 Modulates Neuronal Autophagy and Apoptosis in Cerebral Ischemia–Reperfusion Injury Through the AMPK-mTOR Signaling Pathway

Published:25 November 2024 DOI: 10.1007/s11064-024-04291-w PMID: 39585469
Yingjie Yue, Pingping Chen, Chongwen Ren

Abstract

Cerebral ischemia–reperfusion (I/R) injury is a complex pathophysiological process involving multiple mechanisms, including apoptosis and autophagy, which can lead to significant neuronal damage. PIEZO1, a stretch-activated ion channel, has recently emerged as a potential regulator of cellular responses to ischemic conditions. However, its role in neuronal cell survival and death during ischemic events is not well elucidated. This study aimed to ascertain the regulatory function of PIEZO1 in neuronal cell apoptosis and autophagy in an in vitro model of hypoxia-reoxygenation and an in vivo model of brain I/R injury. HT22 hippocampal neuronal cells were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) to simulate ischemic conditions, with subsequent reoxygenation. In vitro, PIEZO1 expression was silenced using small interfering RNA (si-RNA) transfection. The effects on cell viability, apoptosis, and autophagy were assessed using CCK-8 assays, PI-Annexin/V staining combined with flow cytometry, and Western blot analysis. Additionally, intracellular Ca2+ levels in HT22 cells were measured using a Ca2+ probe. The involvement of the AMPK-mTOR pathway was investigated using rapamycin. For in vivo validation, middle cerebral artery occlusion/reperfusion (MCAO/R) in rats was employed. To determine the neuroprotective role of PIEZO1 silencing, sh-PIEZO1 adeno-associated virus was stereotaxically injected into the cerebral ventricle, and neurological and histological outcomes were assessed?using neurological scoring, TTC staining, H&E staining, Nissl staining, and immunofluorescence. In HT22 cells, OGD/R injury notably upregulated PIEZO1 expression and intracellular Ca2+ levels. Silencing PIEZO1 significantly diminished OGD/R-induced Ca2+ influx, apoptosis, and autophagy, as indicated by lower levels of pro-apoptotic and autophagy-related proteins and improved cell viability. Additionally, PIEZO1 modulated the AMPK-mTOR signaling pathway, an effect that was counteracted by rapamycin treatment, implying its regulatory role. In vivo, PIEZO1 silencing ameliorated brain I/R injury in MCAO/R rats, demonstrated by improved neurological function scores and reduced neuronal apoptosis and autophagy. However, these neuroprotective effects were reversed through rapamycin treatment. Our findings indicate that PIEZO1 is upregulated following ischemic injury and facilitates Ca2+ influx, apoptosis, and autophagy via the AMPK-mTOR pathway. Silencing PIEZO1 confers neuroprotection against I/R injury both in vitro and in vivo, highlighting its potential as a therapeutic target for stroke management.

Graphical Abstract

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 - Inquiry
Rapamycin 53123-88-9 - Inquiry

Similar articles

IF:3

Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats

Saudi Pharmaceutical Journal Wenjie Hu, Xueyan Kuang,etc Published: 1 December 2024
IF:2.6

Sphingosine-1-phosphate receptor 3 promotes neuronal apoptosis via the TNF-α/caspase-3 signaling pathway after acute intracerebral hemorrhage

Molecular and Cellular Neuroscience Dengpan Song, Mengyuan Li,etc Published: 22 November 2024
通化县| 宁蒗| 太仆寺旗| 攀枝花市| 璧山县| 潼关县| 承德县| 永宁县| 花莲市| 广安市| 贵溪市| 乌拉特前旗| 会同县| 连云港市| 微博| 内黄县| 丰原市| 乌拉特后旗| 合作市| 樟树市| 许昌县| 丹寨县| 八宿县| 仙桃市| 万源市| 中山市| 金沙县| 凭祥市| 绥宁县| 南阳市| 任丘市| 黄龙县| 佛坪县| 龙南县| 和林格尔县| 乡宁县| 方山县| 龙里县| 福鼎市| 华亭县| 栖霞市|