title: Mitochondrial oxidative stress index, activity of redox-sensitive aconitase and effects of endogenous anti- and pro-oxidants on its activity in control, Alzheimer's disease and Swedish Familial Alzheimer's disease brain.
abstract: Efficient function of the mitochondrial respiratory chain and the citric acid cycle (CAC) enzymes is required for the maintenance of human brain function. A conception of oxidative stress (OxS) was recently advanced as a disruption of redox signalling and control. Mitochondrial OxS (MOxS) is implicated in the development of Alzheimer's disease (AD). Thus, both pro- and anti-oxidants of the human body and MOxS target primarily the redox-regulated CAC enzymes, like mitochondrial aconitase (MAc). We investigated the specific activity of the MAc and MOxS index (MOSI) in an age-matched control (Co), AD and Swedish Familial AD (SFAD) post-mortem autopsies collected from frontal cortex (FC) and occipital primary cortex (OC) regions of the brain. We also examined whether the mitochondrial neuroprotective signalling molecules glutathione, melatonin and 17-β-estradiol (17βE) and mitochondrially active pro-oxidant neurotoxic amyloid-β peptide can modulate the activity of the MAc isolated from FC and OC regions similarly or differently in the case of Co, AD and SFAD. The activity of redox-sensitive MAc may directly depend on the mitochondrial oxidant/antioxidant balance in age-matched Co, AD and SFAD brain regions.
authors.affiliation: Department of Biochemistry, The Centre of Excellence for Translational Medicine, Tartu University, Estonia.
authors.forename: Marju
authors.initials: M
authors.lastname: Raukas
authors.forename: Reili
authors.initials: R
authors.lastname: Rebane
authors.forename: Riina
authors.initials: R
authors.lastname: Mahlapuu
authors.forename: Viktor
authors.initials: V
authors.lastname: Jefremov
authors.forename: Kersti
authors.initials: K
authors.lastname: Zilmer
authors.forename: Ello
authors.initials: E
authors.lastname: Karelson
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: Mihkel
authors.initials: M
authors.lastname: Zilmer
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D001344:Autopsy; D001921:Brain / Q000187:drug effects / Q000473:pathology; D016022:Case-Control Studies; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017382:Reactive Oxygen Species; D004958:Estradiol; D000154:Aconitate Hydratase; D005978:Glutathione; D008550:Melatonin