机构：[1]Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China[2]Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China大德路总院麻醉科大德路总院麻醉科广东省中医院[3]Department of Anesthesiology, Shenzhen Maternal and Child Health, Hospital of Southern Medical University, Shenzhen, Guangdong, China南方医科大学深圳医院深圳市妇幼保健院深圳市康宁医院深圳医学信息中心[4]Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
Hyperglycemia is considered a risk factor for the enhancement of local anesthetic-induced neurotoxicity. Transient receptor potential melastatin 7 (TRPM7), a kinase-coupled cation channel, has been implicated in a variety of neuropathological processes, including intracellular calcium disturbance and high glucose-induced neuropathy. In this study, we investigated whether TRPM7-related pathophysiology is involved in bupivacaine-induced neurotoxicity in SH-SY5Y cells and how hyperglycemia acts as a risk factor. For initial neurotoxicity evaluation, it was confirmed that cell damage and apoptosis induced by acute exposure to bupivacaine were dependent on its concentration and glucose preconditioning. High glucose preconditioning facilitated the bupivacaine-induced fast and temporary rise in intracellular free calcium concentration ([Ca2+](i)), which was attributed to both calcium influx through TRPM7 and calcium store release. Additionally, bupivacaine was shown to increase TRPM7-like currents, particularly in cells preconditioned with high glucose. Bupivacaine-induced neurotoxicity in hyperglycemia was correlated with extracellular signal-regulated kinase (ERK), but not protein kinase B (AKT) activation. Inhibition of TRPM7 and ERK activity alleviates bupivacaine neurotoxicity. These results suggest that therapeutically targeting TRPM7-related pathophysiological changes could be a potential strategy for treating local anesthetic-induced neurotoxicity exacerbated by hyperglycemia.
基金：
This study was supported by the Doctoral Innovation Project of Shenzhen
Health and Family Planning Commission in 2015 (No. 20150511)
and the Basic Research (free exploration) Project of Shenzhen Science
and Technology Innovation Commission (jcyj201770307091207527).
第一作者机构：[1]Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China[2]Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China[4]Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China[*1]Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, No.253 Gongye Ave., 510282 Guangzhou, China.[*2]Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Chang‐gang‐dong Rd 250, 510260 Guangzhou, China.
推荐引用方式(GB/T 7714)：
Shuang‐Hua Dai,Ya‐Wen Li,Qing‐Xiong Hong,et al.Exaggerated activities of TRPM7 underlie bupivacaine-induced neurotoxicity in the SH-SY5Y cells preconditioned with high glucose[J].JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY.2021,35(8):doi:10.1002/jbt.22826.
APA：
Shuang‐Hua Dai,Ya‐Wen Li,Qing‐Xiong Hong,Tao Su&Shi‐Yuan Xu.(2021).Exaggerated activities of TRPM7 underlie bupivacaine-induced neurotoxicity in the SH-SY5Y cells preconditioned with high glucose.JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY,35,(8)
MLA：
Shuang‐Hua Dai,et al."Exaggerated activities of TRPM7 underlie bupivacaine-induced neurotoxicity in the SH-SY5Y cells preconditioned with high glucose".JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY 35..8(2021)
