TMEM16A Activation Inhibits Autophagy in Dorsal Root Ganglion Cells, Which is Associated with the p38 MAPK/mTOR Pathway.

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Shuyun Yang, Hui Shang, Yuruo Zhang, Jingsong Qiu, Zheyi Guo, Yong Ma, Yuhang Lan, Shaoyang Cui, Hongshuang Tong, Guocai Li
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引用次数: 0

Abstract

Transmembrane member 16A (TMEM16A) exhibits a negative correlation with autophagy, though the underlying mechanism remains elusive. This study investigates the mechanism between TMEM16A and autophagy by inducing autophagy in DRG neuronal cells using Rapamycin. Results indicated that TMEM16A interference augmented cell viability and reduced Rapamycin-induced apoptosis. Autophagosome formation increased with TMEM16A interference but decreased upon overexpression. A similar increase in autophagosomes was observed with SB203580 treatment. Furthermore, TMEM16A interference suppressed Rapamycin-induced gene and protein expression of p38 MAPK and mTOR, whereas overexpression had the opposite effect. These findings suggest that TMEM16A activation inhibits autophagy in DRG cells, which is associated with the p38 MAPK/mTOR pathway, offering a potential target for mitigating neuropathic pain (NP).

TMEM16A激活抑制背根神经节细胞自噬,这与p38 MAPK/mTOR通路有关
跨膜成员16A (TMEM16A)与自噬呈负相关,但其潜在机制尚不清楚。本研究通过使用雷帕霉素诱导DRG神经元细胞自噬来探讨TMEM16A与自噬之间的机制。结果表明,TMEM16A干扰增强了细胞活力,减少了雷帕霉素诱导的细胞凋亡。自噬体的形成在TMEM16A干扰下增加,在过表达时减少。在SB203580处理下观察到类似的自噬体增加。此外,TMEM16A干扰抑制rapamycin诱导的p38 MAPK和mTOR的基因和蛋白表达,而过表达则相反。这些发现表明,TMEM16A激活抑制DRG细胞的自噬,这与p38 MAPK/mTOR通路有关,为减轻神经性疼痛(NP)提供了一个潜在的靶点。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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