title: Caspase-2 and microRNA34a/c regulate lidocaine-induced dorsal root ganglia apoptosis in vitro.
abstract: Epidural administration of lidocaine may cause neurotoxicity in spinal cord dorsal root ganglia neurons (DRGNs). In this study, we explored the underling mechanisms of apoptotic pathways of lidocaine-induced apoptosis in DRGNs. Neonatal rat DRGNs were treated with lidocaine to induced apoptosis in vitro. Western blot showed caspase- (casp-) 2/3/9 proteins were all upregulated by lidocaine in DRGNs. However, inhibition of casp-2 protected lidocaine-induced apoptosis in DRGNs, whereas Casp3/9 inhibition did not. The possible upstream epigenetic regulators of casp-2, microRNA-34 (miR-34) family, including miR-34a/b/c, were evaluated by dual-luciferase reporter assay and qRT-PCR. We found miR-34a/c, but not miR-34b, were down-regulated in lidocaine-induced DRGN apoptosis. Subsequent upregulation of miR-34 family showed miR-34a/c were able to inhibit casp-2 and protect lidocaine-induced apoptosis in DRGNs, whereas miR-34b did not. Thus, out study shows that casp-2, in association with miR-34a/c was actively involved in lidocaine-induced apoptosis in DRGNs. Inhibiting casp-2 or upregulating miR-34a/c may provide novel meanings to protect local anesthetic-induced neurotoxicity.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of JiNing Medical University, JiNing 272000, China. Electronic address: yandong.li@aol.com.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of JiNing Medical University, JiNing 272000, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of JiNing Medical University, JiNing 272000, China.
authors.forename: Laizhu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of JiNing Medical University, JiNing 272000, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of JiNing Medical University, JiNing 272000, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000096:biosynthesis; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008012:Lidocaine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D035683:MicroRNAs / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats
chemical_list: D061945:Caspase Inhibitors; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D034741:RNA, Small Interfering; D008012:Lidocaine; C490359:Casp2 protein, rat; D020169:Caspases; D003546:Cysteine Endopeptidases
keywords: Caspase; Dorsal root ganglion neuron; Lidocaine; Local anesthetic; miR-34