title: High Glucose Enhances Isoflurane-Induced Neurotoxicity by Regulating TRPC-Dependent Calcium Influx.
abstract: Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca2+). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca2+influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca2+influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure. Next, we investigated cytosolic Ca2+concentrations, TRPC mRNA expression levels and tested the effect of the TRPC channel blocker SKF96365 on cytosolic Ca2+levels in cells treated with high glucose or/and isoflurane. Finally, we employed knocked down TRPC6 to demonstrate the role of TRPC in high glucose-mediated enhancement of isoflurane-induced neurotoxicity. The results showed that high glucose could enhance isoflurane-induecd toxic damage in primary hippocampal neurons and SH-SY5Y cells. High glucose enhanced the isoflurane-induced increase of cytosolic Ca2+in SH-SY5Y cells. High glucose elevated TRPC mRNA expression, especially that of TRPC6. SKF96365 and knock down of TRPC6 were able to inhibit the high glucose-induced increase of cytosolic Ca2+and decrease isoflurane-induced neurotoxicity in SH-SY5Y cells cultured with high glucose. Our findings indicate that high glucose could elevate TRPC expression, thus increasing Ca2+influx and enhancing isoflurane-induced neurotoxicity.
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China.
authors.forename: ZhongJie
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China.
authors.forename: ChangQing
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China.
authors.forename: QingGuo
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China.
authors.forename: HongFei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China.
authors.forename: HongYi
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong, China. xushiyuan355@163.com.
authors.forename: ShiYuan
authors.initials: S
authors.lastname: Xu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004357:Drug Synergism; D005947:Glucose / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007530:Isoflurane / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000074287:TRPC6 Cation Channel
chemical_list: D002121:Calcium Channel Blockers; D007093:Imidazoles; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; D007530:Isoflurane; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D005947:Glucose; D002118:Calcium
keywords: Hyperglycemia; Isoflurane; Neurotoxicity; TRPC channels