Dopaminergic neurons in the nigrostriatal system show a pronounced age- related degeneration. Oxidative stress is theorized to precipitate or escalate this neuronal loss. Experiments to test this hypothesis directly by characterizing oxidative damage to proteins and lipids in regions containing these neurons, the putamen and substantia nigra, in postmortem human brain are proposed. In addition, an innovative strategy will be used to compare oxidative stress in dopaminergic and non-dopaminergic neurons in the putamen by measuring damage to proteins and lipids in synaptic vesicles derived from these neurons. Oxidative damage will be measured by biochemical assays for protein carbonyl content, protease sensitivity, and lipid peroxidation products. To assess the function of synaptic vesicles during aging, proton pumping and dopamine storage in the vesicles will be assessed by methods in routine use in this laboratory.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG012993-05
Application #
6201027
Study Section
Project Start
1999-08-01
Project End
2001-04-14
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Type
DUNS #
072933393
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Hewarathna, Asha; Dremina, Elena; Schöneich, Christian (2017) Inhibition and conformational change of SERCA3b induced by Bcl-2. Biochim Biophys Acta Proteins Proteom 1865:121-131
Schöneich, Christian (2016) Thiyl radicals and induction of protein degradation. Free Radic Res 50:143-9
Poole, Leslie B; Schöneich, Christian (2015) Introduction: What we do and do not know regarding redox processes of thiols in signaling pathways. Free Radic Biol Med 80:145-7
Nauser, Thomas; Koppenol, Willem H; Schöneich, Christian (2015) Protein thiyl radical reactions and product formation: a kinetic simulation. Free Radic Biol Med 80:158-63
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Wang, Xinkun; Patel, Nilam D; Hui, Dongwei et al. (2014) Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice. BMC Neurosci 15:37
Jiang, Lei; Bechtel, Misty D; Bean, Jennifer L et al. (2014) Effects of gangliosides on the activity of the plasma membrane Ca2+-ATPase. Biochim Biophys Acta 1838:1255-65
Schöneich, Christian; Dremina, Elena; Galeva, Nadezhda et al. (2014) Apoptosis in differentiating C2C12 muscle cells selectively targets Bcl-2-deficient myotubes. Apoptosis 19:42-57
Wang, Shu-Lin; Sun, Liuchao; Fang, Jianwen (2014) Molecular cancer classification using a meta-sample-based regularized robust coding method. BMC Bioinformatics 15 Suppl 15:S2
Choi, In-Young; Lee, Phil; Wang, Wen-Tung et al. (2014) Metabolism changes during aging in the hippocampus and striatum of glud1 (glutamate dehydrogenase 1) transgenic mice. Neurochem Res 39:446-55

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