title: GSM-900MHz at low dose temperature-dependently downregulates α-synuclein in cultured cerebral cells independently of chaperone-mediated-autophagy.
abstract: The expanding use of GSM devices has resulted in public concern. Chaperone-mediated autophagy (CMA) is a way for protein degradation in the lysosomes and increases under stress conditions as a cell defense response. α-synuclein, a CMA substrate, is a component of Parkinson disease. Since GSM might constitute a stress signal, we raised the possibility that GSM could alter the CMA process. Here, we analyzed the effects of chronic exposure to a low GSM-900MHz dose on apoptosis and CMA. Cultured cerebral cortical cells were sham-exposed or exposed to GSM-900MHz at specific absorption rate (SAR): 0.25W/kg for 24 h using a wire-patch cell. Apoptosis was analyzed by DAPI stain of the nuclei and western blot of cleaved caspase-3. The expression of proteins involved in CMA (HSC70, HSP40, HSP90 and LAMP-2A) and α-synuclein were analyzed by western blot. CMA was also quantified in situ by analyzing the cell localization of active lysosomes. 24 h exposure to GSM-900MHz resulted in ∼0.5°C temperature rise. It did not induce apoptosis but increased HSC70 by 26% and slightly decreased HSP90 (<10%). It also decreased α-synuclein by 24% independently of CMA, since the localization of active lysosomes was not altered. Comparable effects were observed in cells incubated at 37.5°C, a condition that mimics the GSM-generated temperature rise. The GSM-induced changes in HSC70, HSP90 and α-synuclein are most likely linked to temperature rise. We did not observe any immediate effect on cell viability. However, the delayed and long term consequences (protective or deleterious) of these changes on cell fate should be examined.
authors.affiliation: Groupe de Neurobiologie Cellulaire - EA3842 Homéostasie cellulaire et pathologies, Faculté de Médecine, 2 rue du Dr Raymond Marcland, 87025 Limoges Cedex, France. faraj.terro@unilim.fr
authors.forename: Faraj
authors.initials: F
authors.lastname: Terro
authors.forename: Amandine
authors.initials: A
authors.lastname: Magnaudeix
authors.forename: Marion
authors.initials: M
authors.lastname: Crochetet
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bourthoumieu
authors.forename: Cornelia-M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Catherine
authors.initials: C
authors.lastname: Yardin
authors.forename: Philippe
authors.initials: P
authors.lastname: Leveque
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004574:Electromagnetic Fields / Q000009:adverse effects*; D019085:Fluorescent Antibody Technique, Direct; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000502:physiology*; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D018832:Molecular Chaperones; D051844:alpha-Synuclein