Tanshinone IIA Inhibits Glutamate-Induced Oxidative Toxicity through Prevention of Mitochondrial Dysfunction and Suppression of MAPK Activation in SH-SY5Y Human Neuroblastoma Cells

• Published in: Oxidative medicine and cellular longevity Vol. 2017; no. 2017; pp. 1 - 13
• Main Authors: Huang, Zebo, Shi, Ruona, Xiao, Lingyun, Ding, Fei, Wang, Hongyu, Han, Wenjing, Li, Haifeng, Ai, Liping
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01-01-2017; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Adenosine Triphosphate - metabolism; Alzheimer's disease; Apoptosis; Blotting, Western; Care and treatment; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cytotoxicity; Development and progression; Diterpenes, Abietane - pharmacology; Enzymes; Flow Cytometry; Genetic aspects; Glutamic Acid - toxicity; Health aspects; Humans; Kinases; L-Lactate Dehydrogenase - metabolism; Malondialdehyde - metabolism; Membrane Potential, Mitochondrial - drug effects; Neuroblastoma; Neurotoxicity; Oxidative stress; Pharmaceuticals; Protein Carbonylation - drug effects; Protein kinases; Proteins; Quinone; Reactive Oxygen Species - metabolism; Regulation; Rodents; Studies
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2017/4517486

Glutamate excitotoxicity is associated with many neurological diseases, including cerebral ischemia and neurodegenerative diseases. Tanshinone IIA, a diterpenoid naphthoquinone from Salvia miltiorrhiza, has been shown to suppress presynaptic glutamate release, but its protective mechanism against glutamate-induced neurotoxicity is lacking. Using SH-SY5Y human neuroblastoma cells, we show here that excessive glutamate exposure decreases cell viability and proliferation and increases LDH release. Pretreatment with tanshinone IIA, however, prevents the decrease in cell viability and proliferation and the increase in LDH release induced by glutamate. Tanshinone IIA also attenuates glutamate-induced oxidative stress by reducing reactive oxygen species level and malondialdehyde and protein carbonyl contents and by enhancing activities and protein levels of superoxide dismutase and catalase. We then show that tanshinone IIA prevents glutamate-induced mitochondrial dysfunction by increasing mitochondrial membrane potential and ATP content and by reducing mitochondrial protein carbonyl content. Moreover, tanshinone IIA can inhibit glutamate-induced apoptosis through regulation of apoptosis-related protein expression and MAPK activation, including elevation of Bcl-2 protein level, decrease in Bax and cleaved caspase-3 levels, and suppression of JNK and p38 MAPK activation. Collectively, our findings demonstrate that tanshinone IIA protects SH-SY5Y cells against glutamate toxicity by reducing oxidative stress and regulating apoptosis and MAPK pathways.