In vivo protein targets for increased quinoprotein adduct formation in aged substantia nigra.

In vivo protein targets for increased quinoprotein adduct formation in aged substantia nigra. Exp Neurol. 2015 May 5; Authors: Yu G, Liu H, Zhou W, Zhu X, Yu C, Wang N, Zhang Y, Ma J, Zhao Y, Xu Y, Liao L, Ji H, Yuan C, Ma J Abstract The selective vulnerability of dopaminergic neurons in the substantia nigra pars compacta in Parkinson's disease, a late age onset neurodegenerative disorder, indicates the involvement of dopamine metabolism in the pathogenesis. Dopamine oxidation produces dopamine o-quinone, which covalently modifies cysteinyl proteins forming quinoprotein adduct. Although quinoprotein formation correlates with increased dopaminergic neurotoxicity, the in vivo protein targets for quinone modification remain unclear. Using two-dimensional gel electrophoresis and nitroblue tetrazolium/glycinate redox-cycling staining, we compared quinoprotein adducts in substantia nigra of 2- and 15-month old rats and for the first time identified the in vivo protein targets with increased quinone modification in aged substantia nigra. Interestingly, several key enzymes in energy metabolism and mitochondrial function were selectively modified by quinone during aging. In vitro analyses confirmed that two of identified enzymes, L-lactate dehydrogenase (LDH) and malate dehydrogenase (MDH), were readily conjugated by dopamine o-quinone, resulting in a significant reduction in enzyme activity. Since the proteomic approach to detect quinoprotein adducts represents ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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