Neuroprotective effect of ginkgolide B on bupivacaine-induced apoptosis in SH-SY5Y cells.
Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
Le
L
Li
Qing-guo
QG
Zhang
Lu-ying
LY
Lai
Xian-jie
XJ
Wen
Ting
T
Zheng
Chi-wai
CW
Cheung
Shu-qin
SQ
Zhou
Shi-yuan
SY
Xu
D017209:Apoptosis / Q000187:drug effects*; D002045:Bupivacaine / Q000633:toxicity*; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D046934:Ginkgolides / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
D000091342:Endoplasmic Reticulum Chaperone BiP; D046934:Ginkgolides; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007783:Lactones; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C045856:ginkgolide B; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; D053454:Caspase 12; D053148:Caspase 3; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D002045:Bupivacaine