Enhanced expression of WD repeat-containing protein 35 via nuclear factor-kappa B activation in bupivacaine-treated Neuro2a cells.

Enhanced expression of WD repeat-containing protein 35 via nuclear factor-kappa B activation in bupivacaine-treated Neuro2a cells.
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DOI:
10.1371/journal.pone.0086336
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Okada S
Okada S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huang L;Kondo F;Harato M;Feng GG;Ishikawa N;Fujiwara Y;Okada S

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WD重复序列蛋白家族包含大量蛋白质,并且参与多种细胞过程,如信号转导、细胞生长、增殖和凋亡。布比卡因是一种钠通道阻滞剂,用于局部浸润、神经阻滞、硬膜外和鞘内麻醉。最近,我们报道,布比卡因诱导活性氧(ROS)的产生和p38丝裂原活化蛋白激酶(MAPK)的激活,导致在小鼠神经母细胞瘤Neuro2a细胞中的WD重复蛋白35(WDR 35)的表达增加。研究表明,ROS通过磷酸化激活MAPK,随后激活核因子-κ B(NF-κ B)和激活蛋白1(AP-1)。本研究旨在检测NF-κ B和c-Jun/AP-1是否参与布比卡因诱导的Neuro2a细胞WDR 35表达。在Neuro2a细胞中,布比卡因激活NF-κ B和c-Jun。APDC是一种NF-κ B抑制剂,可减弱布比卡因处理的Neuro2a细胞中NF-κ B活性和WDR 35蛋白表达的增加。GW9662是一种选择性过氧化物酶体增殖物激活受体γ拮抗剂,可增强布比卡因处理的Neuro2a细胞中NF-κ B活性和WDR 35蛋白表达的增加。相反,c-Jun siRNA不抑制布比卡因诱导的WDR 35 mRNA表达的增加。这些结果表明,布比卡因诱导Neuro2a细胞中转录因子NF-κ B和c-Jun/AP-1的活化,而NF-κ B的活化参与布比卡因诱导的WDR 35表达的增加。
The family of WD repeat proteins comprises a large number of proteins and is involved in a wide variety of cellular processes such as signal transduction, cell growth, proliferation, and apoptosis. Bupivacaine is a sodium channel blocker administered for local infiltration, nerve block, epidural, and intrathecal anesthesia. Recently, we reported that bupivacaine induces reactive oxygen species (ROS) generation and p38 mitogen-activated protein kinase (MAPK) activation, resulting in an increase in the expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. It has been shown that ROS activate MAPK through phosphorylation, followed by activation of nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). The present study was undertaken to test whether NF-κB and c-Jun/AP-1 are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Bupivacaine activated both NF-κB and c-Jun in Neuro2a cells. APDC, an NF-κB inhibitor, attenuated the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. GW9662, a selective peroxisome proliferator-activated receptor-γ antagonist, enhanced the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. In contrast, c-Jun siRNA did not inhibit the bupivacaine-induced increase in WDR35 mRNA expression. These results indicate that bupivacaine induces the activation of transcription factors NF-κB and c-Jun/AP-1 in Neuro2a cells, while activation of NF-κB is involved in bupivacaine-induced increases in WDR35 expression.
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