PMID- 22185909 OWN - NLM STAT- MEDLINE DCOM- 20120321 LR - 20231213 IS - 1879-3185 (Electronic) IS - 0300-483X (Linking) VI - 292 IP - 2-3 DP - 2012 Feb 26 TI - GSM-900MHz at low dose temperature-dependently downregulates alpha-synuclein in cultured cerebral cells independently of chaperone-mediated-autophagy. PG - 136-44 LID - 10.1016/j.tox.2011.12.003 [doi] AB - 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. alpha-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 alpha-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 approximately 0.5 degrees C temperature rise. It did not induce apoptosis but increased HSC70 by 26% and slightly decreased HSP90 (<10%). It also decreased alpha-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 degrees C, a condition that mimics the GSM-generated temperature rise. The GSM-induced changes in HSC70, HSP90 and alpha-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. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Terro, Faraj AU - Terro F AD - Groupe de Neurobiologie Cellulaire - EA3842 Homeostasie cellulaire et pathologies, Faculte de Medecine, 2 rue du Dr Raymond Marcland, 87025 Limoges Cedex, France. faraj.terro@unilim.fr FAU - Magnaudeix, Amandine AU - Magnaudeix A FAU - Crochetet, Marion AU - Crochetet M FAU - Martin, Ludovic AU - Martin L FAU - Bourthoumieu, Sylvie AU - Bourthoumieu S FAU - Wilson, Cornelia-M AU - Wilson CM FAU - Yardin, Catherine AU - Yardin C FAU - Leveque, Philippe AU - Leveque P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111213 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (HSC70 Heat-Shock Proteins) RN - 0 (HSP90 Heat-Shock Proteins) RN - 0 (LAMP2 protein, human) RN - 0 (Lysosomal-Associated Membrane Protein 2) RN - 0 (Lysosomal Membrane Proteins) RN - 0 (Molecular Chaperones) RN - 0 (alpha-Synuclein) SB - IM MH - Autophagy/*drug effects MH - Blotting, Western MH - Cell Line MH - Cerebral Cortex/cytology/*drug effects/metabolism MH - Down-Regulation/drug effects MH - Electromagnetic Fields/*adverse effects MH - Fluorescent Antibody Technique, Direct MH - HSC70 Heat-Shock Proteins/metabolism MH - HSP90 Heat-Shock Proteins/metabolism MH - Humans MH - Lysosomal-Associated Membrane Protein 2 MH - Lysosomal Membrane Proteins/metabolism MH - Molecular Chaperones/*physiology MH - alpha-Synuclein/*biosynthesis/genetics EDAT- 2011/12/22 06:00 MHDA- 2012/03/22 06:00 CRDT- 2011/12/22 06:00 PHST- 2011/09/21 00:00 [received] PHST- 2011/11/09 00:00 [revised] PHST- 2011/12/05 00:00 [accepted] PHST- 2011/12/22 06:00 [entrez] PHST- 2011/12/22 06:00 [pubmed] PHST- 2012/03/22 06:00 [medline] AID - S0300-483X(11)00508-7 [pii] AID - 10.1016/j.tox.2011.12.003 [doi] PST - ppublish SO - Toxicology. 2012 Feb 26;292(2-3):136-44. doi: 10.1016/j.tox.2011.12.003. Epub 2011 Dec 13.