title: Effects of postmortem delays on protein composition and oxidation.
abstract: Human autopsy brain tissue is widely used to study neurodegenerative diseases such as Alzheimer's, Parkinson's and other diseases. However, when it comes to an evaluation of data obtained from such tissue, it is essential to consider potential postmortem effects on protein composition, posttranslational modification and proteolysis with increasing postmortem delays. In this study, we analyzed mouse brain tissues with different postmortem delays (pmd) of 0 h, 6h and 24h, for changes in protein composition, proteolysis and modifications such as S-nitrosylation, carbonylation and ubiquitination. Proteins involved in Alzheimer's disease (AD) were of special interest, including cytoskeletal and synaptic proteins or proteins involved in inflammation. Several proteins were fairly resistant to degradation during the first 6h but started to degrade thereafter. S-nitrosylation and carbonylation showed not much variation, except for those proteins that were susceptible to degradation. Brain spectrin was S-nitrosylated at death, and S-nitrosylated degradation fragments were measured at a pmd of 24h, indicating a susceptibility of brain spectrin to degradation. Furthermore, the physiological role of S-nitrosylation remains to be investigated. When studying human brain tissue, some proteins are more susceptible to degradation than others, while ubiquitination and carbonylation were little affected during the first 24h after death.
authors.affiliation: Proteomic Unit, Centre for Psychiatric Neuroscience, Department of Psychiatry, CHUV, CERY, CH-1008 Lausanne, Switzerland.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: ElHajj
authors.affiliation: Proteomic Unit, Centre for Psychiatric Neuroscience, Department of Psychiatry, CHUV, CERY, CH-1008 Lausanne, Switzerland.
authors.forename: Amélie
authors.initials: A
authors.lastname: Cachot
authors.affiliation: Proteomic Unit, Centre for Psychiatric Neuroscience, Department of Psychiatry, CHUV, CERY, CH-1008 Lausanne, Switzerland.
authors.forename: Terry
authors.initials: T
authors.lastname: Müller
authors.affiliation: Proteomic Unit, Centre for Psychiatric Neuroscience, Department of Psychiatry, CHUV, CERY, CH-1008 Lausanne, Switzerland.
authors.forename: Irène M
authors.initials: IM
authors.lastname: Riederer
authors.affiliation: Proteomic Unit, Centre for Psychiatric Neuroscience, Department of Psychiatry, CHUV, CERY, CH-1008 Lausanne, Switzerland; Department of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, rue du Bugnon 9, CH-1005 Lausanne, Switzerland. Electronic address: Beat.Riederer@unil.ch.
authors.forename: Beat M
authors.initials: BM
authors.lastname: Riederer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D011180:Postmortem Changes; D050050:Protein Carbonylation / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D003598:Cytoskeletal Proteins; D011506:Proteins; D013049:Spectrin
keywords: Alzheimer’s disease; Brain spectrin; Carbonylation; Postmortem delay; S-nitrosylation; Ubiquitination