Enhanced expression of WD repeat-containing protein 35 via nuclear factor-kappa B activation in bupivacaine-treated Neuro2a cells.
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.
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Lei
L
Huang
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Fumio
F
Kondo
Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Misako
M
Harato
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Guo-Gang
GG
Feng
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Naoshisa
N
Ishikawa
Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Yoshihiro
Y
Fujiwara
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Shoshiro
S
Okada
D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D015870:Gene Expression / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics
D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; C558597:WDR35 protein, mouse; D002045:Bupivacaine