Bupivacaine-induced cytotoxicity related to endoplasmic reticulum stress pathways in SH-SY5Y cells

Title
Bupivacaine-induced cytotoxicity related to endoplasmic reticulum stress pathways in SH-SY5Y cells
Authors
강주희
Keywords
Local anesthetics, Bupivacaine, Neurotoxicity, ER stress, Caspase, L-Carnosine
Issue Date
2013
Publisher
MOLECULAR & CELLULAR TOXICOLOGY
Series/Report no.
MOLECULAR & CELLULAR TOXICOLOGY ; Vol.9 no.2 Startpage 141 Endpage 147
Abstract
Spinal anesthesia with local anesthetics (LAs) can cause toxic effects on the central nervous system, leading to postoperative neurological complications. Although previous studies have suggested that LAs cause ion channel block and mitochondrial dysfunction followed by neuronal cell death, the mechanisms underlying LA toxicity are not fully understood. In this study, we evaluated the neurotoxic mechanisms of bupivacaine and lidocaine related to endoplasmic reticulum (ER) stress using the SH-SY5Y human neuronal cell line. At clinical concentrations used during regional anesthesia, both bupivacaine and lidocaine significantly reduced cell viability in a concentrationdependent manner and differentially induced ER stress responses, including the rapid induction of Grp78 and CHOP expression and phosphorylation of c-jun N-terminal kinase (JNK), p-38 mitogen-activated protein kinase (MAPK) and eukaryotic initiation factor 2 alpha (eIF2α). CHOP induction by bupivacaine and lidocaine was inhibited with a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580), indicating that apoptotic CHOP expression was mediated by JNK and p38 MAPK activation. In addition, bupivacaine-induced apoptotic cell death was dependent on caspase 3 activity. Bupivacaine cytotoxicity was significantly but not completely inhibited by an endogenous dipeptide, L-carnosine. In conclusion, LAs cause acute ER stress responses and caspase 3-dependent cell death, which can be prevented with the pharmacological chaperone dipeptide L-carnosine.
URI
http://dspace.inha.ac.kr/handle/10505/31304
ISSN
1738-642X
Appears in Collections:
Medical School/College of Medicine (의학전문대학원/의과대학) > Medical Science (의학) > Journal Papers, Reports(의학 논문, 보고서)
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