Differential Proteomics Analysis of Specific Carbonylated Proteins in the Temporal Cortex of Aged Rats: The Deterioration of Antioxidant System

Wang, Qingsong; Zhao, Xuyang; He, Sizhi; Liu, Yashu; An, Malaviya; Ji, Jianguo

doi:10.1007/s11064-009-0023-8

Cited by 21 publications

(22 citation statements)

References 50 publications

(79 reference statements)

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“…These changes correlated with age related deterioration in learning and memory 145 . An age associated increase in the carbonylation of aconitase and ATP synthase is found in rats as well 146 69,147 . In addition, adenine nucleotide translocator, voltage-dependent anion channel, glutamate oxaloacetate transaminase, and aconitase are more susceptible to oxidative stress induced carbonylation in the mitochondria of aged rat brain 148 .…”

Section: Biological Consequences Of Protein Oxidationmentioning

confidence: 91%

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Proteomic Identification of Carbonylated Proteins and Their Oxidation Sites

2010

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Excessive oxidative stress leaves a protein carbonylation fingerprint in biological systems. Carbonylation is an irreversible post translational modification (PTM) that often leads to the loss of protein function and can be a component of multiple diseases. Protein carbonyl groups can be generated directly (by amino acids oxidation and the a-amidation pathway) or indirectly by forming adducts with lipid peroxidation products or glycation and advanced glycation end-products. Studies of oxidative stress are complicated by the low concentration of oxidation products and wide array of routes by which proteins are carbonylated. The development of new selection and enrichment techniques coupled with advances in mass spectrometry are allowing identification of hundreds of new carbonylated protein products from a broad range of proteins located at many sites in biological systems. The focus of this review is on the use of proteomics tools and methods to identify oxidized proteins along with specific sites of oxidative damage and the consequences of protein oxidation.

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Section: Biological Consequences Of Protein Oxidationmentioning

confidence: 91%

“…150 Carbonyl levels of ten proteins increased significantly in the temporal cortex of aged rats has been observed as well. 151 …”

Section: Biological Consequences Of Protein Oxidationmentioning

confidence: 99%

Proteomic Identification of Carbonylated Proteins and Their Oxidation Sites

2010

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“…In a differential proteomic analysis, PRX 1 from aged rat temporal cortex tissue is carbonylated, suggesting that this enzyme contributes to the decline in cognitive function that occurs during aging (431). PRX II also has been shown to be upregulated in response to increase Ab levels during AD, with the purpose of protecting neurons against Ab-induced toxicity (456).…”

Section: Massaad and Klannmentioning

confidence: 99%

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Massaad

Klann

2011

Antioxidants & Redox Signaling

471

350

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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 number of experimental evidence indicate that increased rate of free radical generation and decreased efficiency of the reparative/degradative mechanisms, such as proteolysis, both are factors which primarily contribute to age-related elevation in the level of oxidative stress and brain damage. With respect to this, it has been suggested that decreases in levels of enzymes which ordinarily protect neuronal cells against oxidative stress with age may be responsible for increased levels of free-radical damage in the brain, or that these enzymes themselves are susceptible to inactivation by free radical molecules which increase with age in the brain [27]. During aging a number of enzymes accumulate as catalytically inactive or less active forms.…”

Section: The ''Free Radical Hypothesis'' Of Agingmentioning

confidence: 99%

Cellular Stress Responses, Mitostress and Carnitine Insufficiencies as Critical Determinants in Aging and Neurodegenerative Disorders: Role of Hormesis and Vitagenes

et al. 2010

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The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. A prediction of this theory is that, among species, differential rates of aging may be apparent on the basis of intrinsic differences in oxidative damage accrual. Although widely accepted, there is a growing number of exceptions to this theory, most contingently related to genetic model organism investigations. Proteins are one of the prime targets for oxidative damage and cysteine residues are particularly sensitive to reversible and irreversible oxidation. The adaptation and survival of cells and organisms requires the ability to sense proteotoxic insults and to coordinate protective cellular stress response pathways and chaperone networks related to protein quality control and stability. The toxic effects that stem from the misassembly or aggregation of proteins or peptides, in any cell type, are collectively termed proteotoxicity. Despite the abundance and apparent capacity of chaperones and other components of homeostasis to restore folding equilibrium, the cell appears poorly adapted for chronic proteotoxic stress which increases in cancer, metabolic and neurodegenerative diseases. Pharmacological modulation of cellular stress response pathways has emerging implications for the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. A critical key to successful medical intervention is getting the dose right. Achieving this goal can be extremely challenging due to human inter-individual variation as affected by age, gender, diet, exercise, genetic factors and health status. The nature of the dose response in and adjacent to the therapeutic zones, over the past decade has received considerable advances. The hormetic dose-response, challenging long-standing beliefs about the nature of the dose-response in a lowdose zone, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses, including carnitines. This paper describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including the possible signaling mechanisms by which the carnitine system, by interplaying metabolism, mitochondrial energetics and activation of critical vitagenes, modulates signal transduction cascades that confer cytoprotection against chronic degenerative damage associated to aging and neurodegenerative disorders.

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Differential Proteomics Analysis of Specific Carbonylated Proteins in the Temporal Cortex of Aged Rats: The Deterioration of Antioxidant System

Cited by 21 publications

References 50 publications

Proteomic Identification of Carbonylated Proteins and Their Oxidation Sites

Proteomic Identification of Carbonylated Proteins and Their Oxidation Sites

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Cellular Stress Responses, Mitostress and Carnitine Insufficiencies as Critical Determinants in Aging and Neurodegenerative Disorders: Role of Hormesis and Vitagenes

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