Lingyang Chen1, Xiaodan Wang1, Wenguang Huang1, Tingting Ying1, Minjuan Chen1, Jianbin Cao1, Mingcang Wang2. 1. Department of Anesthesia, Zhejiang Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou 317000, China. 2. Department of Anesthesia, Zhejiang Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou 317000, China. Electronic address: wang_zhiming@aol.com.
Abstract
PURPOSE: Anesthetic reagents, such as bupivacaine (Bv), induce significant neurotoxicity in dorsal root ganglion neurons (DRGNs). In this study, we investigated the expression, function and cross-association of microRNA-137-3p (miR-137-3p) and lysine (K)-specific demethylase 1A (LSD1) in a murine model of Bv-induced neural injury in DRGNs. METHODS: Murine DRGNs were culture in vitro and treated with Bv. QPCR was used to evaluate miR-137-3p expression in Bv-injured DRGNs. MiR-137-3p was genetically downregulated to evaluate its rescuing effect on Bv-induced DRGN apoptosis and neurite retraction. The association of miR-137-3p on its downstream target, LSD1 coding gene KDM1A, was evaluated by dual-luciferase activity assay and qPCR. In miR-137-3p-downregulated DRGNs, KDM1A was inhibited to evaluate its involvement in miR-137-3p-mediated modulation on Bv-induced DRGN neurotoxicity. Furthermore, KDM1A expression in Bv-injured DRGN was evaluated by qPCR, and LSD1 was overexpressed in DRGN to evaluate its direct effect on Bv-induced neurotoxicity. RESULTS: MiR-137-3p was upregulated in Bv-injured DRGNs. MiR-137-3p downregulation rescued Bv-induced DRGN apoptosis and neurite retraction. LSD1 was demonstrated to be downstream to, and inversely modulated by miR-137-3p in DRGN. In Bv-injured DRGNs, LSD1 downregulation reversed miR-137-3p-downregualtion-induced neural protection. Furthermore, LSD1 upregulation directly rescued Bv-induced apoptosis and neurite retraction in DRGNs. CONCLUSIONS: MiR-137-3p and its downstream target LSD1 are inversely associated to regulate anesthetics-induced neurotoxicity in DRGN. This signaling pathway may be a therapeutic candidate to reduce anesthetics-induced neurological damage in human patients.
PURPOSE: Anesthetic reagents, such as bupivacaine (Bv), induce significant neurotoxicity in dorsal root ganglion neurons (DRGNs). In this study, we investigated the expression, function and cross-association of microRNA-137-3p (miR-137-3p) and lysine (K)-specific demethylase 1A (LSD1) in a murine model of Bv-induced neural injury in DRGNs. METHODS:Murine DRGNs were culture in vitro and treated with Bv. QPCR was used to evaluate miR-137-3p expression in Bv-injured DRGNs. MiR-137-3p was genetically downregulated to evaluate its rescuing effect on Bv-induced DRGN apoptosis and neurite retraction. The association of miR-137-3p on its downstream target, LSD1 coding gene KDM1A, was evaluated by dual-luciferase activity assay and qPCR. In miR-137-3p-downregulated DRGNs, KDM1A was inhibited to evaluate its involvement in miR-137-3p-mediated modulation on Bv-induced DRGN neurotoxicity. Furthermore, KDM1A expression in Bv-injured DRGN was evaluated by qPCR, and LSD1 was overexpressed in DRGN to evaluate its direct effect on Bv-induced neurotoxicity. RESULTS:MiR-137-3p was upregulated in Bv-injured DRGNs. MiR-137-3p downregulation rescued Bv-induced DRGN apoptosis and neurite retraction. LSD1 was demonstrated to be downstream to, and inversely modulated by miR-137-3p in DRGN. In Bv-injured DRGNs, LSD1 downregulation reversed miR-137-3p-downregualtion-induced neural protection. Furthermore, LSD1 upregulation directly rescued Bv-induced apoptosis and neurite retraction in DRGNs. CONCLUSIONS:MiR-137-3p and its downstream target LSD1 are inversely associated to regulate anesthetics-induced neurotoxicity in DRGN. This signaling pathway may be a therapeutic candidate to reduce anesthetics-induced neurological damage in humanpatients.
Authors: Emmett E Whitaker; Brianne Z Wiemann; Jason C Xia; Bruno Bissonnette; Joseph Liu; Paolo Fadda; Joseph D Tobias; Fievos L Christofi Journal: J Anesth Date: 2019-10-14 Impact factor: 2.078