SOD3 Ameliorates Aβ25-35-Induced Oxidative Damage in SH-SY5Y Cells by Inhibiting the Mitochondrial Pathway.
This study was designed to investigate the protective effects of extracellular superoxide dismutase (SOD3) against amyloid beta (Aβ25-35)-induced damage in human neuroblastoma SH-SY5Y cells and to elucidate the mechanisms responsible for this beneficial effect. SH-SY5Y cells overexpressing SOD3 were generated by adenoviral vector-mediated infection and Aβ25-35was then added to the cell culture system to establish an in vitro model of oxidative stress. Cell viability, the generation of intracellular reactive oxygen species (ROS), the expression and activity of antioxidant enzymes, the levels of lipid peroxidation malondialdehyde (MDA), the expression of mitochondrial apoptosis-related genes and calcium images were examined. Following Aβ25-35exposure, SOD3 overexpression promoted the survival of SH-SY5Y cells, decreased the production of ROS, decreased MDA and calcium levels, and decreased cytochrome c, caspase-3, caspase-9 and Bax gene expression. Furthermore, SOD3 overexpression increased the expression and activity of antioxidant enzyme genes and Bcl-2 expression. Together, our data demonstrate that SOD3 ameliorates Aβ25-35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial pathway. These data provide new insights into the functional actions of SOD3 on oxidative stress-induced cell damage.
Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.
Rong
R
Yang
Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 400020, China.
Li
L
Wei
Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.
Qing-Qing
QQ
Fu
Affiliated Hospital of the Academy of Military Medical Sciences, Beijing, 100071, China. youhua307@163.com.
Hua
H
You
Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China. huarongyu2003@163.com.
Hua-Rong
HR
Yu
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D013482:Superoxide Dismutase; D002118:Calcium
Antioxidant enzymes; Extracellular superoxide dismutase; Mitochondrial pathway; Oxidative stress; Reactive oxygen species