Overexpression of zinc-α2-glycoprotein suppressed seizures and seizure-related neuroflammation in pentylenetetrazol-kindled rats.
Overexpression of zinc-α2-glycoprotein suppressed seizures and seizure-related neuroflammation in pentylenetetrazol-kindled rats.
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锌-α2-糖蛋白的过度表达抑制戊四唑点燃大鼠的癫痫发作和癫痫相关的神经炎症
DOI：
10.1186/s12974-018-1132-6
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发表时间：
2018-03-22
影响因子：
9.3
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Liu Y;Wang T;Liu X;Wen Y;Xu T;Yu X;Wei X;Ding X;Mo L;Yin M;Tan X;Chen L
锌-α2-糖蛋白（ZAG）是一种42 kDa的蛋白质，据报道是一种抗炎脂肪细胞因子。临床和实验研究表明，脑炎症在癫痫的发生和发作中起重要作用。有趣的是，ZAG与许多重要的炎症介质的密切关系已被证明。我们以前的研究发现ZAG在神经元中存在，并发现ZAG在癫痫中减少，并与TGFβ和ERK相互作用。本研究旨在探讨ZAG在癫痫发作中的作用及其对癫痫相关神经炎症的影响。通过腺相关病毒载体注射方法在大鼠海马内过表达AZGP 1，观察戊四氮（PTZ）点燃后大鼠的癫痫发作行为和脑电图。测定典型炎症介质TNFα、IL-6、TGFβ、ERK和ERK磷酸化水平。AZGP 1过表达可减轻戊四氮所致癫痫发作的严重程度，延长点燃潜伏期，减轻癫痫样放电。过表达AZGP 1还可抑制PTZ点燃大鼠TNFα、IL-6、TGFβ和ERK磷酸化的表达。ZAG可抑制TGFβ介导的ERK磷酸化，抑制TNFα和IL-6介导的神经炎症，提示ZAG可能通过抑制神经炎症抑制癫痫发作。ZAG可能是一个潜在的新的癫痫治疗靶点。
Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein reported as an anti-inflammatory adipocytokine. Evidences from clinical and experimental studies revealed that brain inflammation plays important roles in epileptogenesis and seizure. Interestingly, closely relationship between ZAG and many important inflammatory mediators has been proven. Our previous study identified ZAG in neurons and found that ZAG is decreased in epilepsy and interacts with TGFβ and ERK. This study aimed to investigate the role of ZAG in seizure and explore its effect on seizure-related neuroinflammation. We overexpressed AZGP1 in the hippocampus of rats via adeno-associated virus vector injection and observed their seizure behavior and EEG after pentylenetetrazol (PTZ) kindling. The level of typical inflammation mediators including TNFα, IL-6, TGFβ, ERK, and ERK phosphorylation were determined. The overexpression of AZGP1 reduced the seizure severity, prolonged the latency of kindling, and alleviated epileptiform discharges in EEG changes induced by PTZ. Overexpression of AZGP1 also suppressed the expression of TNFα, IL-6, TGFβ, and ERK phosphorylaton in PTZ-kindled rats. ZAG may inhibit TGFβ-mediated ERK phosphorylation and inhibit neuroinflammation mediated by TNFα and IL-6, suggesting ZAG may suppress seizure via inhibiting neuroinflammation. ZAG may be a potential and novel therapeutic target for epilepsy.
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DOI：
10.1073/pnas.90.3.975
发表时间：
1993-02-01
影响因子：
11.1
作者：
ITOH, T;KAIBUCHI, K;TAKAI, Y
通讯作者：
TAKAI, Y
2型糖尿病患者中循环的锌 - 葡萄糖共转运蛋白2（SGLT2）抑制剂增加了循环的锌-α2-糖蛋白水平。
影响因子：
4.6
作者：
Liao X;Wang X;Li H;Li L;Zhang G;Yang M;Yuan L;Liu H;Yang G;Gao L
通讯作者：
Gao L
影响因子：
9.3
作者：
Chuang YC;Lin TK;Huang HY;Chang WN;Liou CW;Chen SD;Chang AY;Chan SH
通讯作者：
Chan SH
影响因子：
3.5
作者：
Lehtimaki, K. A.;Keranen, T.;Peltola, J.
通讯作者：
Peltola, J.
影响因子：
2.5
作者：
Cunningham, AJ;Murray, CA;OConnor, JJ
通讯作者：
OConnor, JJ