title: Far-infrared radiation protects viability in a cell model of Spinocerebellar Ataxia by preventing polyQ protein accumulation and improving mitochondrial function.
abstract: Far infrared radiation (FIR) is currently investigated as a potential therapeutic strategy in various diseases though the mechanism is unknown. Presently, we tested if FIR mediates beneficial effects in a cell model of the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3). SCA3 is caused by a mutation leading to an abnormal polyglutamine expansion (PolyQ) in ataxin-3 protein. The consequent aggregation of mutant ataxin-3 results in disruption of vital cell functions. In this study, neuroblastoma cells (SK-N-SH) was transduced to express either non-pathogenic ataxin-3-26Q or pathogenic ataxin-3-78Q proteins. The cells expressing ataxin-3-78Q demonstrated decreased viability, and increased sensitivity to metabolic stress in the presence rotenone, an inhibitor of mitochondrial respiration. FIR exposure was found to protect against these effects. Moreover, FIR improved mitochondrial respiratory function, which was significantly compromised in ataxin-3-78Q and ataxin-3-26Q expressing cells. This was accompanied by decreased levels of mitochondrial fragmentation in FIR treated cells, as observed by fluorescence microscopy and protein expression analysis. Finally, the expression profile LC3-II, Beclin-1 and p62 suggested that FIR prevent the autophagy inhibiting effects observed in ataxin-3-78Q expressing cells. In summary, our results suggest that FIR have rescuing effects in cells expressing mutated pathogenic ataxin-3, through recovery of mitochondrial function and autophagy.
authors.affiliation: Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50094, Taiwan.
authors.forename: Jui-Chih
authors.initials: JC
authors.lastname: Chang
authors.affiliation: Department of Neurology, Changhua Christian Hospital, Changhua 50094, Taiwan.
authors.forename: Shey-Lin
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hoel
authors.affiliation: Department of Neurology, Changhua Christian Hospital, Changhua 50094, Taiwan.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Changhua Christian Hospital, Changhua 50094, Taiwan.
authors.forename: Ko-Hung
authors.initials: KH
authors.lastname: Liu
authors.affiliation: Department of Life Science, Tunghai University, Taichung 40704, Taiwan.
authors.forename: Mingli
authors.initials: M
authors.lastname: Hsieh
authors.affiliation: Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.
authors.forename: August
authors.initials: A
authors.lastname: Hoel
authors.affiliation: Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.
authors.forename: Karl Johan
authors.initials: KJ
authors.lastname: Tronstad
authors.affiliation: Department of Dermatology, Changhua Christian Hospital, Changhua 50094, Taiwan.
authors.forename: Kuo-Chia
authors.initials: KC
authors.lastname: Yan
authors.affiliation: Department of Chinese Medicine, Obstetrics and Gynecology, Dermatology, and Urology, China Medical University Hospital, Taichung 40447, Taiwan.|School of Chinese Medicine, Graduate Institute of Integrated Medicine, Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 40447, Taiwan.
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: School of Chinese Medicine, Graduate Institute of Integrated Medicine, Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 40447, Taiwan.|Departments of Medical Research, Obstetrics and Gynecology, Dermatology, and Urology, China Medical University Hospital, Taichung 40447, Taiwan.
authors.forename: Wei-Yong
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Department of Surgery, Changhua Christian Hospital, Changhua 50094, Taiwan.
authors.forename: Shou-Jen
authors.initials: SJ
authors.lastname: Kuo
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua 50094, Taiwan.|Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Shih-Li
authors.initials: SL
authors.lastname: Su
authors.affiliation: Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50094, Taiwan.|Department of Neurology, Changhua Christian Hospital, Changhua 50094, Taiwan.|School of Chinese Medicine, Graduate Institute of Integrated Medicine, Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 40447, Taiwan.
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
mesh_terms: D000067699:Ataxin-3; D001343:Autophagy / Q000528:radiation effects; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D007259:Infrared Rays; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects*; D063154:Mitochondrial Dynamics / Q000528:radiation effects; D008954:Models, Biological; D018384:Oxidative Stress / Q000528:radiation effects; D010101:Oxygen Consumption / Q000528:radiation effects; D010455:Peptides / Q000378:metabolism*; D020754:Spinocerebellar Ataxias / Q000473:pathology*
chemical_list: D010455:Peptides; C097188:polyglutamine; D000067699:Ataxin-3