title: High membrane protein oxidation in the human cerebral cortex.
abstract: Oxidative stress is thought to be one of the main mediators of neuronal damage in human neurodegenerative disease. Still, the dissection of causal relationships has turned out to be remarkably difficult. Here, we have analyzed global protein oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins in three different mammalian species: aged human cortex and cerebellum from patients with or without Alzheimer's disease, mouse cortex and cerebellum from young and old animals, and adult rat hippocampus and cortex subjected or not subjected to cerebral ischemia. Most tissues showed relatively similar levels of protein oxidation. However, human cortex was affected by severe membrane protein oxidation, while exhibiting lower than average cytoplasmic protein oxidation. In contrast, ex vivo autooxidation of murine cortical tissue primarily induced aqueous protein oxidation, while in vivo biological aging or cerebral ischemia had no major effect on brain protein oxidation. The unusually high levels of membrane protein oxidation in the human cortex were also not predicted by lipid peroxidation, as the levels of isoprostane immunoreactivity in human samples were considerably lower than in rodent tissues. Our results indicate that the aged human cortex is under steady pressure from specific and potentially detrimental membrane protein oxidation. The pronounced difference between humans, mice and rats regarding the primary site of cortical oxidation might have contributed to the unresolved difficulties in translating into therapies the wealth of data describing successful antioxidant neuroprotection in rodents.
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Granold
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Electronic address: moosmann@uni-mainz.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Moosmann
authors.affiliation: Department of Anesthesiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Staib-Lasarzik
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.affiliation: Institute of Physiology and Pathophysiology, Philipps University, Marburg, Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Del Rey
authors.affiliation: Department of Anesthesiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelhard
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Behl
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Parvana
authors.initials: P
authors.lastname: Hajieva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D050050:Protein Carbonylation; D051381:Rats; D013045:Species Specificity
chemical_list: D008565:Membrane Proteins
keywords: Aging; Alzheimer's disease; Animal models; Neurodegeneration; Oxidative stress; Protein oxidation