Capillarisin protects SH-SY5Y cells against bupivacaine-induced apoptosis via ROS-mediated PI3K/PKB pathway

Autor: Qian Wang, Tongxin Zhao
Rok vydání: 2020
Předmět:
0301 basic medicine
Cell Survival
Apoptosis
Oxidative phosphorylation
medicine.disease_cause
030226 pharmacology & pharmacy
General Biochemistry
Genetics and Molecular Biology
Superoxide dismutase
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
medicine
Humans
Mitochondrial respiratory chain complex I
Viability assay
General Pharmacology
Toxicology and Pharmaceutics
Endoplasmic Reticulum Chaperone BiP
chemistry.chemical_classification
Membrane Potential
Mitochondrial
Reactive oxygen species
biology
Chemistry
General Medicine
Endoplasmic Reticulum Stress
Molecular biology
Bupivacaine
Mitochondria
Oxidative Stress
030104 developmental biology
Mitochondrial respiratory chain
Chromones
biology.protein
Phosphatidylinositol 3-Kinase
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Oxidative stress
Zdroj: Life sciences. 259
ISSN: 1879-0631
Popis: Aims Bupivacaine, a common local anesthetic, can induce neurotoxicity and neurological complications. Capillarisin, a bioactive ingredient of Artemisia capillaris root extracts, has been reported to protect SH-SY5Y cells against oxidative stress-mediated neuronal cell death. Nevertheless, the effects of capillarisin on bupivacaine-induced neurotoxicity in SH-SY5Y cells remain unclear. Main methods Cell viability, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, and apoptosis were detected. Malondialdehyde (MDA) content, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities were measured for evaluation of oxidative stress. Western blot was performed to detect the changes of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB) pathway, and expression of cleaved poly ADP ribose polymerase (PARP), cleaved caspase-3, glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). Activities of mitochondrial respiratory chain complexes I-III and adenosine triphosphate (ATP) content were measured to evaluate mitochondrial damage. Key findings Bupivacaine treatment dose-dependently reduced cell viability, increased LDH release, and induced ROS production and PI3K/PKB pathway inactivation in SH-SY5Y cells, which were overturned by capillarisin treatment. Capillarisin inhibited bupivacaine-induced apoptosis in SH-SY5Y cells by decreasing cleaved PARP and cleaved caspase-3 expression. Capillarisin inhibited bupivacaine-induced oxidative stress, decrease of mitochondrial respiratory chain complex I, II, and III activities and ATP content, and increase of GRP78 and CHOP expression in SH-SY5Y cells. However, treatment with LY294002 abolished the effects of capillarisin on bupivacaine-induced neurotoxicity in SH-SY5Y cells. Significance Capillarisin protected SH-SY5Y cells against bupivacaine-induced apoptosis by inhibiting oxidative stress, mitochondrial injury, and endoplasmic reticulum stress via ROS-mediated of PI3K/PKB pathway.
Databáze: OpenAIRE
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