Induction of endoplasmic reticulum (ER) stress and caspase-dependent neuronal cell injury by bupivacaine in SH-SY5Y cells

초록

Local anesthetics are well known to cause neurotoxicity such as cauda equine syndrome. For example, lidocaine increased intracellular calcium concentration to toxic level followed by mitochondrial injury and apoptosis-related mitogen-activated protein kinase (MAPK) activation. However, the cytotoxic mechanisms of bupivacaine are unknown. Here, we evaluated the effects of bupivacaine on the cell viability and the expression of endoplasmic reticulum (ER) stress response proteins in SH-SY5Y human neuroblastoma cell line, SH-SY5Y. Our results showed that bupivacaine and lidocaine induced ER stress responses and apoptosis-related proteins, and activated c-Jun N-terminal kinase (JNK) and p38 MAPK. In addition, bupivacaine increased the activity of caspase-3. Bupivacaine decreased cell viability in a dose-dependent manner. The cytotoxicity of bupivacaine was significantly inhibited by a specific caspase-3 inhibitor. In conclusion, our results indicate that bupivacaine-induced ER stress response may be a cytotoxic mechanism, and that caspase-3 inhibitor may be useful to prevent the bupivacaine-induced neuronal injury.