Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells

BMC Neuroscience

Shoshiro Okada¹  Yoshihiro Fujiwara²  Naohisa Ishikawa¹  Jun-Hua Fan¹  Guo-Gang Feng¹  Koji Tsunekawa¹  Fumio Kondo¹  Lei Huang¹  Misako Harato² 

[1] Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan;Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan

关键词: p38 MAPK;    Reactive oxygen species;    Bupivacaine;    Neuro2a cells;    WDR35;   

Others  :  1140695
DOI  :  10.1186/1471-2202-13-149

 received in 2012-07-20, accepted in 2012-12-07,  发布年份 2012

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Harato et al.; licensee BioMed Central Ltd.

【 图 表 】

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