Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells.
Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells.
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DOI：
10.1186/1471-2202-13-149
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发表时间：
2012-12-10
期刊：
影响因子：
2.4
通讯作者：
Okada S
中科院分区：
文献类型：
--
作者：
Harato M;Huang L;Kondo F;Tsunekawa K;Feng GG;Fan JH;Ishikawa N;Fujiwara Y;Okada S
布比卡因诱导的神经毒性已被证明是通过细胞凋亡发生的。最近，布比卡因被证明可以在人神经母细胞瘤细胞系中引发活性氧 (ROS) 产生并诱导细胞凋亡，同时激活 p38 丝裂原激活蛋白激酶 (MAPK)。我们报道了 WDR35（一种 WD40 重复蛋白）可能通过 caspase-3 激活介导细胞凋亡。本研究旨在测试布比卡因是否诱导小鼠神经母细胞瘤 Neuro2a 细胞凋亡，并确定 ROS、p38 MAPK 和 WDR35 是否参与其中。我们的结果表明，布比卡因诱导 Neuro2a 细胞中 ROS 生成和 p38 MAPK 激活，导致细胞凋亡。布比卡因还以剂量和时间依赖性方式增加 WDR35 表达。过氧化氢 (H2O2) 也会增加 Neuro2a 细胞中 WDR35 的表达。抗氧化剂 (EUK-8) 和 p38 MAPK 抑制剂 (SB202190) 治疗减弱了布比卡因或 H2O2 诱导的 caspase-3 活性、细胞死亡和 WDR35 表达的增加。虽然用 WDR35 siRNA 转染 Neuro2a 细胞减弱了布比卡因或 H2O2 诱导的 WDR35 mRNA 和蛋白表达的增加，但与我们之前的研究相反，它并没有抑制布比卡因或 H2O2 处理的细胞中 caspase-3 活性的增加。总之，我们的结果表明布比卡因诱导 Neuro2a 细胞凋亡。布比卡因诱导 ROS 生成和 p38 MAPK 激活，导致这些细胞中 WDR35 表达增加。然而，WDR35 表达的增加对于布比卡因诱导的 Neuro2a 细胞凋亡可能不是必需的。这些结果可能表明，Neuro2a 细胞中存在另一种独立于 WDR35 表达的布比卡因诱导细胞凋亡机制。
Bupivacaine-induced neurotoxicity has been shown to occur through apoptosis. Recently, bupivacaine was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in a human neuroblastoma cell line. We have reported that WDR35, a WD40-repeat protein, may mediate apoptosis through caspase-3 activation. The present study was undertaken to test whether bupivacaine induces apoptosis in mouse neuroblastoma Neuro2a cells and to determine whether ROS, p38 MAPK, and WDR35 are involved. Our results showed that bupivacaine induced ROS generation and p38 MAPK activation in Neuro2a cells, resulting in apoptosis. Bupivacaine also increased WDR35 expression in a dose- and time-dependent manner. Hydrogen peroxide (H2O2) also increased WDR35 expression in Neuro2a cells. Antioxidant (EUK-8) and p38 MAPK inhibitor (SB202190) treatment attenuated the increase in caspase-3 activity, cell death and WDR35 expression induced by bupivacaine or H2O2. Although transfection of Neuro2a cells with WDR35 siRNA attenuated the bupivacaine- or H2O2-induced increase in expression of WDR35 mRNA and protein, in contrast to our previous studies, it did not inhibit the increase in caspase-3 activity in bupivacaine- or H2O2-treated cells. In summary, our results indicated that bupivacaine induced apoptosis in Neuro2a cells. Bupivacaine induced ROS generation and p38 MAPK activation, resulting in an increase in WDR35 expression, in these cells. However, the increase in WDR35 expression may not be essential for the bupivacaine-induced apoptosis in Neuro2a cells. These results may suggest the existence of another mechanism of bupivacaine-induced apoptosis independent from WDR35 expression in Neuro2a cells.
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影响因子：
9.8
作者：
Werdehausen, R.;Fazeli, S.;Stevens, M. F.
通讯作者：
Stevens, M. F.
影响因子：
7.6
作者：
Lee, S. J.;Shin, T. J.;Kim, H. J.
通讯作者：
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影响因子：
5
作者：
Huang, L;Hotta, Y;Shimada, Y
通讯作者：
Shimada, Y
影响因子：
8.8
作者：
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通讯作者：
Samii, K
DOI：
10.1016/j.bbrc.2010.02.133
发表时间：
2010-03-26
影响因子：
3.1
作者：
Feng, Guo-Gang;Li, Chang;Ishikawa, Naohisa
通讯作者：
Ishikawa, Naohisa