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

Autor: Jui-Chih Chang, Tsu-Shing Wang, Haw-Wen Chen, Yu-Ling Wu, Chin-San Liu, Mingli Hsieh, Chien-Chun Li, Wei-Yong Lin, Kai-Li Liu
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
congenital
hereditary
and neonatal diseases and abnormalities
Cell Survival
lcsh:Medicine
Apoptosis
Resveratrol
medicine.disease_cause
Antioxidants
Article
Animals
Genetically Modified
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Caffeic Acids
Cell Line
Tumor
medicine
Autophagy
Animals
Humans
lcsh:Science
chemistry.chemical_classification
Membrane Potential
Mitochondrial
Reactive oxygen species
Multidisciplinary
Chemistry
Caspase 3
lcsh:R
Neurotoxicity
NF-kappa B
Machado-Joseph Disease
medicine.disease
Cell biology
Disease Models
Animal
Oxidative Stress
030104 developmental biology
Biochemistry
Cell culture
Spinocerebellar ataxia
Drosophila
lcsh:Q
Tumor Suppressor Protein p53
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
Zdroj: Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
Scientific Reports
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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