Intracellular ion and protein nanoparticle-induced osmotic pressure modify astrocyte swelling and brain edema in response to glutamate stimuli.
Intracellular ion and protein nanoparticle-induced osmotic pressure modify astrocyte swelling and brain edema in response to glutamate stimuli.
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细胞内离子和蛋白质纳米颗粒诱导的渗透压改变了星形胶质细胞响应谷氨酸刺激的肿胀和脑水肿。
DOI：
10.1016/j.redox.2019.101112
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发表时间：
2019
期刊：
影响因子：
11.4
通讯作者：
Guo Jun
中科院分区：
文献类型：
--
作者：
Zhang JiaRui;Wang YuXuan;Zheng ZiHui;Sun XiaoHe;Chen TingTing;Li Chen;Zhang XiaoLong;Guo Jun
细胞内张力活性在细胞毒性脑水肿和星形胶质细胞肿胀中起重要作用。在这里，一些基因编码的基于FRET的张力探针被设计用来光学检测细胞骨架结构的张力，包括它们的大小和向量。星形胶质细胞肿胀导致GFAP张力升高，这与内向微丝(MFS)和微管力(MTS)的拮抗作用有关。在谷氨酸诱导的星形胶质细胞肿胀中，GFAP张力升高是由于外向离子和蛋白纳米颗粒诱导的渗透压(PN-OP)增加，其中PN-OP可以通过MF和MT的解聚、蛋白质纳米颗粒的产生以及Cofilin和stathmin-1的激活而引起。联合用药降低离子渗透压和PN-OP，与自由基清除剂一起，减轻了体内的脑水肿。研究表明，细胞内渗透压(尤其是PN-OP)在谷氨酸诱导的星形胶质细胞肿胀和脑水肿中起着关键作用。细胞质电位的恢复是开发新药和治疗脑水肿的一个有前途的靶点。
Intracellular tension activity plays a crucial role in cytotoxic brain edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and protein nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, protein nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and brain edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure brain edema.