Aberrant Neuronal and Mitochondrial Proteins in Hippocampus of Transgenic Mice Overexpressing Human Cu/Zn Superoxide Dismutase 1

Shin, Joo‐Ho; London, Jacqueline; Pêcheur, M.; Höger, Harald; Pollak, Daniela D.; Lubec, Gert

doi:10.1016/j.freeradbiomed.2004.05.019

Cited by 40 publications

(33 citation statements)

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“…Oxidation of EF-Tu mt has been previously described in synaptosomes incubated with Aβ peptide, suggesting that this protein is particularly susceptible to oxidation, and probably involved in the pathogenesis of AD (Boyd-Kimball et al, 2005). Interestingly, transgenic mice overexpressing human Cu 2+ /Zn 2+ superoxide dismutase 1 (Tg-SOD1), a condition associated to increased reactive species production, present lower levels of EF-Tu mt , mitochondrial swelling and vacuolization in the hippocampus (Shin et al, 2004). However, whether decreases in the amount of EF-Tu mt or its oxidation, such as the one described in this study and previous studies from our group (Boyd-Kimball et al, 2005), are causally related to the morphologic and functional mitochondrial alterations associated to oxidative stress in TgSOD1 mice, is still undefined.…”

Section: Discussionmentioning

confidence: 99%

Acrolein induces selective protein carbonylation in synaptosomes

et al. 2007

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Acrolein, the most reactive of the α,β-unsaturated aldehydes, is endogenously produced by lipid peroxidation, and has been found increased in the brain of patients with Alzheimer's disease. Although it is known that acrolein increases total protein carbonylation and impairs the function of selected proteins, no study has addressed which proteins are selectively carbonylated by this aldehyde. In this study we investigated the effect of increasing concentrations of acrolein (0, 0.005, 0.05, 0.5, 5, 50 μM) on protein carbonylation in gerbil synaptosomes. In addition, we applied proteomics to identify synaptosomal proteins that were selectively carbonylated by 0.5 μM acrolein. Acrolein increased total protein carbonylation in a dose-dependent manner. Proteomic analysis (2-D electrophoresis followed by mass spectrometry) revealed that tropomyosin-3-gamma isoform 2, tropomyosin-5, β-actin, mitochondrial Tu translation elongation factor (EFTu mt ) and voltagedependent anion channel (VDAC) were significantly carbonylated by acrolein. Consistent with the proteomics studies that have identified specifically oxidized proteins in Alzheimer's Disease (AD) brain, the proteins identified in this study are involved in a wide variety of cellular functions including energy metabolism, neurotransmission, protein synthesis, and cytoskeletal integrity. Our results suggest that acrolein may significantly contribute for oxidative damage in AD brain.Acrolein (2-propen-1-al), the most reactive of the α,β-unsaturated aldehydes (Esterbauer et al., 1991), is a toxic compound found in automobile exhaust gases, overheated cooking oils and a metabolite of cyclophosphamide and allyl alcohol (Halliwell and Gutteridge, 1999). Acrolein can also be endogenously produced as a product of lipid peroxidation (Adams and Klaidman, 1993,Uchida, 1999) and from polyamine metabolism (Takano et al., 2005 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 July 13. Published in final edited form as:Neuroscience. 2007 July 13; 147(3): 674-679. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript . As a consequence, the identification of acrolein adducts has been proposed as a biologic marker for oxidative stress (Kehrer and Biswal, 2000). Accordingly, acrolein levels have been found increased in pathological conditions associated with oxidative stress, such as spinal cord injury (Luo et al., 2005), diabetic nephropathy (Suzuki and Miyata, 1999) and Alzheimer's Disease (AD) (Markesbery and Lovell, 1998,Cal...

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Section: Discussionmentioning

confidence: 99%

Acrolein induces selective protein carbonylation in synaptosomes

et al. 2007

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“…The level of key synaptosomal proteins in the hippocampus is significantly reduced in mice overexpressing SOD-1 (140,387), suggesting that the beneficial quenching of superoxide may be outweighed by the predominant presence of H 2 O 2 , which has been shown to possess neurotoxic effects. This idea is supported by studies of SOD-1 overexpression during AD or TBI.…”

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Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Massaad

Klann

2011

Antioxidants & Redox Signaling

454

326

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The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age-or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function.

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“…A necessary step to confirm their existence is to obtain evidence of gene or protein expression. As a result, some previously annotated hypothetical genes were regarded as "expressed or known genes" after their expression or functional data were available (Saha et al, 2002;Kolker et al, 2004;Redman et al, 2004;Shin et al, 2004;Prasad et al, 2005;Xiao et al, 2005). Therefore, hypothetical genes should be regarded as a mixture of functional and misannotated genes or pseudogenes.…”

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Expansion Mechanisms and Functional Annotations of Hypothetical Genes in the Rice Genome

Jiang

Christoffels²,

Ramamoorthy³

et al. 2009

Plant Physiology

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In each completely sequenced genome, 30% to 50% of genes are annotated as uncharacterized hypothetical genes. In the rice (Oryza sativa) genome, 10,918 hypothetical genes were annotated in the latest version (release 6) of the Michigan State University rice genome annotation. We have implemented an integrative approach to analyze their duplication/expansion and function. The analyses show that tandem/segmental duplication and transposition/retrotransposition have significantly contributed to the expansion of hypothetical genes despite their different contribution rates. A total of 3,769 hypothetical genes have been detected from retrogene, tandem, segmental, Pack-MULE, or long terminated direct repeat-related duplication/ expansion. The nonsynonymous substitutions per site and synonymous substitutions per site analyses showed that 21.65% of them were still functional, accounting for 7.47% of total hypothetical genes. Global expression analyses have identified 1,672 expressed hypothetical genes. Among them, 415 genes might function in a developmental stage-specific manner. Antisense strand expression and small RNA analyses have demonstrated that a high percentage of these hypothetical genes might play important roles in negatively regulating gene expression. Homologous searches against Arabidopsis (Arabidopsis thaliana), maize (Zea mays), sorghum (Sorghum bicolor), and indica rice genomes suggest that most of the hypothetical genes could be annotated from recently evolved genomic sequences. These data advance the understanding of rice hypothetical genes as being involved in lineage-specific expansion and that they function in a specific developmental stage. Our analyses also provide a valuable means to facilitate the characterization and functional annotation of hypothetical genes in other organisms.

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Aberrant Neuronal and Mitochondrial Proteins in Hippocampus of Transgenic Mice Overexpressing Human Cu/Zn Superoxide Dismutase 1

Cited by 40 publications

References 35 publications

Acrolein induces selective protein carbonylation in synaptosomes

Acrolein induces selective protein carbonylation in synaptosomes

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Expansion Mechanisms and Functional Annotations of Hypothetical Genes in the Rice Genome

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