Increase of autophagy and attenuation of apoptosis by Salvigenin promote survival of SH-SY5Y cells following treatment with H₂O₂.
Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. Here, we tried to elucidate the possible neuroprotective effect of Salvigenin, a natural polyphenolic compound, on oxidative stress-induced apoptosis and autophagy in human neuroblastoma SH-SY5Y cells. We measured cell viability by MTT test and found that 25 μM is the best protective concentration of Salvigenin. GSH and SOD assays suggested that Salvigenin activates antioxidant factors. At the same time, measurement of ER stress-associated proteins including calpain and caspase-12 showed the ability of Salvigenin to decrease ER stress. We found that Salvigenin could decrease the apoptotic factors. Salvigenin inhibited H(2)O(2)-induced caspase-3 which is a hallmark of apoptosis in addition to reducing Bax\Bcl-2 ratio by 1.45 fold. Additionally, Salvigenin increased the levels of autophagic factors. Our results showed an increase in LC3-II/LC3-I ratio, Atg7, and Atg12 in the presence of 25 μM of Salvigenin by about 1.28, 1.25, and 1.54 folds, respectively, compared to H(2)O(2)-treated cells. So it seems that H(2)O(2) cytotoxicity mainly results from apoptosis. Besides, Salvigenin helps cells to survive by inhibiting apoptosis and enhancing autophagy that opens a new horizon for the future experiments.
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Ghazaleh
G
Rafatian
Fariba
F
Khodagholi
Mahdi Moridi
MM
Farimani
Shahnaz Babaei
SB
Abraki
Mossa
M
Gardaneh
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D047309:Flavones; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; C014049:salvigenin; D006861:Hydrogen Peroxide