AMPK attenuates bupivacaine-induced neurotoxicity.
Bupivacaine has been widely used as a long-acting local anesthetic. However, evidence strongly suggests that bupivacaine causes apoptosis. AMP-activated protein kinase (AMPK) regulates metabolic homeostasis and mediates cellular protection from stress. We hypothesized that AMPK may be cytoprotective in bupivacaine-treated Schwann cells. To explore this, we applied bupivacaine to the RT4-D6P2T Schwann cell line. The expression of phosphorylated AMPK was compared after bupivacaine treatment. Bupivacaine induced cell death in a time- and dose- [50% lethal dose (LD(50)) = 316 microM] dependent manner, and increased expression of phosphorylated AMPK after bupivacaine treatment. Bupivacaine-induced cytotoxicity was attenuated by AICAR (an AMPK activator), whereas compound C (an AMPK inhibitor) enhanced it. The cytoprotective effect of AICAR was reversed in the presence of iodotubercidin, an AICAR inhibitor. Our results suggest that the AMPK pathway may protect Schwann cells from bupivacaine-induced cytotoxicity.
Lee
S J
SJ
Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, 28 Yeongeon-dong Jongno-gu, Seoul 110-768, Republic of Korea.
Shin
T J
TJ
Kang
I S
IS
Ha
J H
JH
Lee
S C
SC
Kim
H J
HJ
D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000502:physiology*; D000108:Acetylcarnitine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000633:toxicity*; D017209:Apoptosis; D002045:Bupivacaine / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D006801:Humans; D016015:Logistic Models; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012583:Schwann Cells / Q000187:drug effects*; D015854:Up-Regulation
D000779:Anesthetics, Local; D020536:Enzyme Activators; D018696:Neuroprotective Agents; D000108:Acetylcarnitine; D055372:AMP-Activated Protein Kinases; D002045:Bupivacaine