Inhibition of DNA Repair Protein Ku70 in High-Glucose Environment Aggravates the Neurotoxicity Induced by Bupivacaine in SH-SY5Y Cells

Bupivacaine, a common local anesthetic, causes serious nerve injury, especially in diabetic patients, as high glucose has been reported to enhance bupivacaine-induced neurotoxicity. However, the key regulator for synergism remains unknown. To our surprise, the expression of repair protein Ku70 is su...

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Bibliographic Details
Published in:BioMed research international 2020, Vol.2020 (2020), p.1-10
Main Authors: Liang, Gen-qiang, Li, Shuang, Wang, Hui, Zhou, Yu, Ji, Zhong-Hua, Mao, Jun
Format: Article
Language:English
Subjects:
Anesthetics
Apoptosis
Bupivacaine
Caspase-3
Cytotoxicity
Damage
Deoxyribonucleic acid
Dextrose
Diabetes
Diabetes mellitus
Diabetics
DNA
DNA damage
DNA repair
Ethylenediaminetetraacetic acid
Genomes
Glucose
Hyperglycemia
Kinases
Local anesthetics
Mammals
Medical research
Microscopy
Neurotoxicity
Nucleic acids
Proteins
Reactive oxygen species
Repair
Synergism
Toxicity
Transcription
Variance analysis
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Summary:Bupivacaine, a common local anesthetic, causes serious nerve injury, especially in diabetic patients, as high glucose has been reported to enhance bupivacaine-induced neurotoxicity. However, the key regulator for synergism remains unknown. To our surprise, the expression of repair protein Ku70 is suppressed, while the high-glucose environment induces DNA oxidative damage in neurons. Here, we aim to investigate whether the inhibition of Ku70 by high-glucose conditions aggrandized bupivacaine-induced DNA damage. Consistent with previous results, bupivacaine induced reactive oxygen species production and upregulated Ku70 and cleaved caspase-3 expressions at both transcript and protein levels and ultimately caused nucleic acid damage and apoptosis in human neuroblastoma (SH-SY5Y) cells. High-glucose treatment inhibited the expression of Ku70 and enhanced bupivacaine-induced neurotoxicity. In contrast, the overexpression of Ku70 mitigated DNA damage and apoptosis triggered by bupivacaine and high glucose. In conclusion, our data indicated that local anesthetics may aggravate nerve toxicity in a high-glucose environment.
ISSN:2314-6133
2314-6141
DOI:10.1155/2020/1283214