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Rotenone Upregulates Alpha-Synuclein and Myocyte Enhancer Factor 2D Independently from Lysosomal Degradation Inhibition
Joint Authors
Sala, Gessica
Arosio, Alessandro
Stefanoni, Giovanni
Melchionda, Laura
Riva, Chiara
Marinig, Daniele
Brighina, Laura
Ferrarese, Carlo
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-07-30
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Dysfunctions of chaperone-mediated autophagy (CMA), the main catabolic pathway for alpha-synuclein, have been linked to the pathogenesis of Parkinson’s disease (PD).
Since till now there is limited information on how PD-related toxins may affect CMA, in this study we explored the effect of mitochondrial complex I inhibitor rotenone on CMA substrates, alpha-synuclein and MEF2D, and effectors, lamp2A and hsc70, in a human dopaminergic neuroblastoma SH-SY5Y cell line.
Rotenone induced an upregulation of alpha-synuclein and MEF2D protein levels through the stimulation of their de novo synthesis rather than through a reduction of their CMA-mediated degradation.
Moreover, increased MEF2D transcription resulted in higher nuclear protein levels that exert a protective role against mitochondrial dysfunction and oxidative stress.
These results were compared with those obtained after lysosome inhibition with ammonium chloride.
As expected, this toxin induced the cytosolic accumulation of both alpha-synuclein and MEF2D proteins, as the result of the inhibition of their lysosome-mediated degradation, while, differently from rotenone, ammonium chloride decreased MEF2D nuclear levels through the downregulation of its transcription, thus reducing its protective function.
These results highlight that rotenone affects alpha-synuclein and MEF2D protein levels through a mechanism independent from lysosomal degradation inhibition.
American Psychological Association (APA)
Sala, Gessica& Arosio, Alessandro& Stefanoni, Giovanni& Melchionda, Laura& Riva, Chiara& Marinig, Daniele…[et al.]. 2013. Rotenone Upregulates Alpha-Synuclein and Myocyte Enhancer Factor 2D Independently from Lysosomal Degradation Inhibition. BioMed Research International،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-1031003
Modern Language Association (MLA)
Sala, Gessica…[et al.]. Rotenone Upregulates Alpha-Synuclein and Myocyte Enhancer Factor 2D Independently from Lysosomal Degradation Inhibition. BioMed Research International No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-1031003
American Medical Association (AMA)
Sala, Gessica& Arosio, Alessandro& Stefanoni, Giovanni& Melchionda, Laura& Riva, Chiara& Marinig, Daniele…[et al.]. Rotenone Upregulates Alpha-Synuclein and Myocyte Enhancer Factor 2D Independently from Lysosomal Degradation Inhibition. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-1031003
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1031003