The induction of amyloid precursor protein and alpha-synuclein in rat hippocampal astrocytes by diethyldithiocarbamate and copper with or without glutathione.
alpha-Synuclein is the major component of Lewy bodies. Its aggregation can be accelerated by copper, iron, or beta-amyloid (Abeta) and has been thought to provide a nucleation center during the formation of amyloid plaques. The main structural component of amyloid plaque is Abeta, which is derived from a larger protein, amyloid precursor protein (APP). Xenobiotics have been implicated in the etiology of the neurodegenerative disease. Mechanisms of diethyldithiocarbamate (DDC) neurotoxicity involve copper chelation and interactions with SH groups resulting in oxidative stress. In this study, rat hippocampal astrocytes were treated with DDC (75 microM), CuCl(2) (0.2 microM), or DDC (75 microM) plus CuCl(2) (0.2 microM) for 1h. Cells were allowed to recover with or without 10 mM GSH. Results showed an increase of APP and alpha-synuclein production occurring in a time-dependent manner. At 4 h post-treatment, cells contained small positively stained material deposited throughout the cytosol for APP and by 8 h post-treatment increases were seen in both APP and alpha-synuclein. Immunoblots supported immunocytochemical results. Glutathione (GSH) decreased the accumulation of these proteins at 8 h post-treatment.
Cheng
S Y
SY
College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
Trombetta
L D
LD
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003300:Copper / Q000633:toxicity*; D003599:Cytoskeleton / Q000502:physiology; D004050:Ditiocarb / Q000633:toxicity*; D005978:Glutathione / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051843:Synucleins; D051844:alpha-Synuclein
D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D003300:Copper; D004050:Ditiocarb; D005978:Glutathione