Treatment with Caffeic Acid and Resveratrol Alleviates Oxidative Stress Induced Neurotoxicity in Cell and Drosophila Models of Spinocerebellar Ataxia Type3

• Published in: Scientific reports Vol. 7; no. 1; pp. 11641 - 12
• Main Authors: Wu, Yu-Ling, Chang, Jui-Chih, Lin, Wei-Yong, Li, Chien-Chun, Hsieh, Mingli, Chen, Haw-Wen, Wang, Tsu-Shing, Liu, Chin-San, Liu, Kai-Li
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 14.09.2017; Nature Publishing Group UK
• Subjects: Animals; Animals, Genetically Modified; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Ataxia; Ataxin; Autophagy - drug effects; Butyl hydroperoxide; Caffeic acid; Caffeic Acids - pharmacology; Caspase 3 - metabolism; Cell culture; Cell Line, Tumor; Cell Survival - drug effects; Disease Models, Animal; Drosophila; Humans; Insects; Locomotor activity; Machado-Joseph disease; Machado-Joseph Disease - drug therapy; Machado-Joseph Disease - etiology; Machado-Joseph Disease - metabolism; Membrane Potential, Mitochondrial - drug effects; Neurotoxicity; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Oxidative Stress - drug effects; p53 Protein; Phagocytosis; Polyglutamine; Reactive oxygen species; Reactive Oxygen Species - metabolism; Resveratrol; Resveratrol - pharmacology; Trinucleotide repeat diseases; Tumor Suppressor Protein p53 - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11839-0

Spinocerebellar ataxia type 3 (SCA3) is caused by the expansion of a polyglutamine (polyQ) repeat in the protein ataxin-3 which is involved in susceptibility to mild oxidative stress induced neuronal death. Here we show that caffeic acid (CA) and resveratrol (Res) decreased reactive oxygen species (ROS), mutant ataxin-3 and apoptosis and increased autophagy in the pro-oxidant tert-butyl hydroperoxide (tBH)-treated SK-N-SH-MJD78 cells containing mutant ataxin-3. Furthermore, CA and Res improved survival and locomotor activity and decreased mutant ataxin-3 and ROS levels in tBH-treated SCA3 Drosophila. CA and Res also altered p53 and nuclear factor-κB (NF-κB) activation and expression in tBH-treated cell and fly models of SCA3, respectively. Blockade of NF-κB activation annulled the protective effects of CA and Res on apoptosis, ROS, and p53 activation in tBH-treated SK-N-SH-MJD78 cells, which suggests the importance of restoring NF-κB activity by CA and Res. Our findings suggest that CA and Res may be useful in the management of oxidative stress induced neuronal apoptosis in SCA3.