Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

Tannu, Nilesh S; Mash, Deborah C.; Hemby, Scott E.

doi:10.1038/sj.mp.4001914

Cited by 36 publications

(40 citation statements)

References 123 publications

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“…23 It is important to note that the membrane fraction was not included in the current analysis primarily due to the limitations of 2DG for analyzing membrane proteins. 35 Most hydrophobic (membrane-bound) proteins are insoluble in nondetergent sample buffer used for isoelectric focusing (IEF) and the ones which are soluble precipitate at their respective isoelectric points (pI).…”

Section: Protein Isolation and Fractionationmentioning

confidence: 99%

“…Tissue proteins were fractionated as described previously. 13,23,24,34 Fractionation enables the enrichment of low abundance proteins in distinct cellular fractions compared to total cell/tissue homogenate and therefore allows increased coverage of the analyzed proteome.…”

Section: Protein Isolation and Fractionationmentioning

confidence: 99%

“…Experiment 1: Differential native protein expression using 2D-DIGE Cyanine dye labeling-Minimal labeling of the lysine residues was achieved by reaction with cyanine dyes, as described previously. 23,36,37 Briefly, a normalization (pooled) sample was prepared by combining 50 μg from each sample. The labeling of 50 μg of protein sample (each sample) was optimized by labeling with 200 pmol of appropriate dye (suspended in > 99.5% pure dimethylformamide).…”

Section: Protein Isolation and Fractionationmentioning

confidence: 99%

“…23 The abundances of proteins from several families were found to be significantly altered, including proteins belonging to cell structure, synaptic plasticity/signal transduction, mitochondrial function and metabolic pathways. Interestingly, several of the proteins were functionally associated with N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, previously shown to be increased in the VTA and NAc of cocaine overdose victims.…”

Section: Introductionmentioning

confidence: 99%

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Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

2008

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The reinforcing effects and long-term consequences of cocaine self-administration have been associated with brain regions of the mesolimbic dopamine pathway, namely the nucleus accumbens (NAc). Studies of cocaine-induced biochemical adaptations in rodent models have advanced our knowledge; however, unbiased detailed assessments of intracellular alterations in the primate brain are scarce, yet essential, to develop a comprehensive understanding of cocaine addiction. To this end, two-dimensional difference in gel electrophoresis (2D-DIGE) was used to compare changes in cytosolic protein abundance in the NAc between rhesus monkeys selfadministering cocaine and controls. Following image normalization, spots with significantly differential image intensities (P < 0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser-desorption ionization time-of-flight time-of-flight (MALDI-TOF-TOF). In total, 1098 spots were subjected to statistical analysis with 22 spots found to be differentially abundant of which 18 proteins were positively identified by mass spectrometry. In addition, approximately 1000 protein spots were constitutively expressed of which 21 proteins were positively identified by mass spectrometry. Increased levels of proteins in the cocaine-exposed monkeys include glial fibrillary acidic protein, syntaxin-binding protein 3, protein kinase C isoform, adenylate kinase isoenzyme 5 and mitochondrial-related proteins, whereas decreased levels of proteins included β-soluble N-ethylmaleimide-sensitive factor attachment protein and neural and non-neural enolase. Using a complimentary proteomics approach, the differential expression of phosphorylated proteins in the cytosolic fraction of these subjects was examined. Two-dimensional gel electrophoresis (2DGE) was followed by gel staining with Pro-Q Diamond phosphoprotein gel stain, enabling differentiation of approximately 150 phosphoprotein spots between the groups. Following excision and trypsin digestions, MALDI-TOF-TOF was used to confirm the identity of 15 cocaine-altered phosphoproteins. Significant increased levels were detected for γ-aminobutyric acid type A receptor-associated protein 1, 14-3-3 γ-protein, glutathione S-transferase and brain-type aldolase, whereas significant decreases were observed for β-actin, Rab GDP-dissociation inhibitor, guanine deaminase, peroxiredoxin 2 isoform b and Results from these studies indicate coordinated dysregulation of proteins related to cell structure, signaling, metabolism and mitochondrial function. These data extend and compliment previous studies of cocaine-induced biochemical alterations in human post-mortem brain tissue, using an animal model that closely recapitulates the human condition and provide new insight into the molecular basis of the disease and potential targets for pharmacotherapeutic intervention.

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Section: Protein Isolation and Fractionationmentioning

confidence: 99%

Section: Protein Isolation and Fractionationmentioning

confidence: 99%

Section: Protein Isolation and Fractionationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

2008

Self Cite

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“…The proteome of the NAC has also been explored in cocaine abusers (107) and in self-administering Rhesus monkeys (108) . Consistent with the concept of drug-induced plasticity in this region of the human brain, several proteins associated with synaptic plasticity were found to have altered levels in cocaine abusers.…”

Section: Protein Expression Studiesmentioning

confidence: 99%

The effect of alcohol and nicotine abuse on gene expression in the brain

Flatscher-Bader

Wilce

2009

Nutr. Res. Rev.

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Alcohol intake at levels posing an acute heath risk is common amongst teenagers. Alcohol abuse is the second most common mental disorder worldwide. The incidence of smoking is decreasing in the Western world but increasing in developing countries and is the leading cause of preventable death worldwide. Considering the longstanding history of alcohol and tobacco consumption in human societies, it might be surprising that the molecular mechanisms underlying alcohol and smoking dependence are still incompletely understood. Effective treatments against the risk of relapse are lacking. Drugs of abuse exert their effect manipulating the dopaminergic mesocorticolimbic system. In this brain region, alcohol has many potential targets including membranes and several ion channels, while other drugs, for example nicotine, act via specific receptors or binding proteins. Repeated consumption of drugs of abuse mediates adaptive changes within this region, resulting in addiction. The high incidence of alcohol and nicotine co-abuse complicates analysis of the molecular basis of the disease. Gene expression profiling is a useful approach to explore novel drug targets in the brain. Several groups have utilised this technology to reveal drug-sensitive pathways in the mesocorticolimbic system of animal models and in human subjects. These studies are the focus of the present review.

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Neuroproteomics and its applications in research on nicotine and other drugs of abuse

2007

Proteomics Clinical Apps

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The rapidly growing field of neuroproteomics is able to track changes in protein expression and protein modifications underlying various physiological conditions, including the neural diseases related to drug addiction. Thus, it presents great promise in characterizing protein function, biochemical pathways, and networks to understand the mechanisms underlying drug dependence. In this article, we first provide an overview of proteomics technologies and bioinformatics tools available to analyze proteomics data. Then we summarize the recent applications of proteomics to profile the protein expression pattern in animal or human brain tissues after the administration of nicotine, alcohol, amphetamine, butorphanol, cocaine, and morphine. By comparing the protein expression profiles in response to chronic nicotine exposure with those appearing in response to treatment with other drugs of abuse, we identified three biological processes that appears to be regulated by multiple drugs of abuse: energy metabolism, oxidative stress response, and protein degradation and modification. Such similarity indicates that despite the obvious differences among their chemical properties and the receptors with which they interact, different substances of abuse may cause some similar changes in cellular activities and biological processes in neurons.

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Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

Cited by 36 publications

References 123 publications

Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

The effect of alcohol and nicotine abuse on gene expression in the brain

Neuroproteomics and its applications in research on nicotine and other drugs of abuse

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