Activation of the TRPV1 cation channel contributes to stress-induced astrocyte migration.

Activation of the TRPV1 cation channel contributes to stress-induced astrocyte migration.
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TRPV1阳离子通道的激活有助于压力诱导的星形胶质细胞迁移。

DOI:
10.1002/glia.22691
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发表时间:
2014-09
期刊:
影响因子:
6.2
通讯作者:
Calkins, David J.
Calkins, David J.
中科院分区:
医学1区
文献类型:
--
作者:
Ho, Karen W.;Lambert, Wendi S.;Calkins, David J.

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星形胶质细胞在正常生理学中为神经元提供代谢、结构和突触支持,并且还广泛参与应激或损伤反应的致病过程。反应性星形胶质细胞可以通过各种潜在调节剂介导的细胞内 Ca2+ 变化进行细胞骨架重组并增加迁移。在这里,我们测试了机械损伤(划伤)后分离的视网膜星形胶质细胞的迁移是否涉及瞬时受体电位香草酸-1通道(TRPV1),该通道有助于Ca2+介导的细胞骨架重排和其他系统中的迁移。使用 TRPV1 特异性拮抗剂辣椒西平 (CPZ) 或 5'-碘树脂毒素 (IRTX),可将迁移速度减慢多达 44%,具体取决于浓度。相比之下,用 TRPV1 特异性激动剂、辣椒素 (CAP) 或树脂毒素 (RTX) 处理,在一定浓度范围内仅产生轻微的加速作用。细胞外 Ca2+ 与 EGTA (1 mM) 的螯合使星形胶质细胞迁移减慢了 35%。比率成像表明,划伤导致星形胶质细胞 Ca2+ 急剧增加 20%,并且随着距伤口的距离增加而消散。 IRTX 治疗既减缓并显着减少了划痕引起的 Ca2+ 增加。 CPZ 和 IRTX 都会影响星形胶质细胞的细胞骨架组织,特别是在伤口边缘附近。综上所述,我们的结果表明,星形胶质细胞响应机械应力的动员涉及细胞外 Ca2+ 的流入和部分由 TRPV1 激活介导的细胞骨架变化。
Astrocytes provide metabolic, structural and synaptic support to neurons in normal physiology and also contribute widely to pathogenic processes in response to stress or injury. Reactive astrocytes can undergo cytoskeletal reorganization and increase migration through changes in intracellular Ca2+ mediated by a variety of potential modulators. Here we tested whether migration of isolated retinal astrocytes following mechanical injury (scratch wound) involves the transient receptor potential vanilloid-1 channel (TRPV1), which contributes to Ca2+-mediated cytoskeletal rearrangement and migration in other systems. Application of the TRPV1-specific antagonists, capsazepine (CPZ) or 5’-iodoresiniferatoxin (IRTX), slowed migration by as much as 44%, depending on concentration. In contrast, treatment with the TRPV1-specific agonists, capsaicin (CAP) or resiniferatoxin (RTX) produced only a slight acceleration over a range of concentrations. Chelation of extracellular Ca2+ with EGTA (1 mM) slowed astrocyte migration by 35%. Ratiometric imaging indicated that scratch wound induced a sharp 20% rise in astrocyte Ca2+ that dissipated with distance from the wound. Treatment with IRTX both slowed and dramatically reduced the scratch-induced Ca2+ increase. Both CPZ and IRTX influenced astrocyte cytoskeletal organization, especially near the wound edge. Taken together, our results indicate that astrocyte mobilization in response to mechanical stress involves influx of extracellular Ca2+ and cytoskeletal changes in part mediated by TRPV1 activation.
DOI: 10.1006/bbrc.1998.9592
发表时间: 1998-11-09
影响因子: 3.1
作者:
Bouvard, D;Block, MR
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DOI: 10.1046/j.1432-1327.2000.01463.x
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期刊: EUROPEAN JOURNAL OF BIOCHEMISTRY
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