Differential modulation of apoptosis-associated proteins by ethanol in rat cerebral cortex and cerebellum

Rajgopal, Yadavalli; Chetty, C. S.; Vemuri, Mohan C.

doi:10.1016/s0014-2999(03)01795-3

Cited by 28 publications

(23 citation statements)

References 34 publications

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“…A variety of proteins involved in the apoptotic cascade were expressed in the cortex of alcohol-treated rats (Rajgopal et al 2003). In the human PFC, we noted the over expression of TIMP3, which has been associated with angiogenesis and neurogliomas (Huang et al 2000;Qi et al 2003).…”

Section: Discussionmentioning

confidence: 93%

Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics

Flatscher-Bader

Brug

Hwang

et al. 2005

Journal of Neurochemistry

143

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The molecular processes underlying alcohol dependence are not fully understood. Many characteristic behaviours result from neuroadaptations in the mesocorticolimbic system. In addition, alcoholism is associated with a distinct neuropathology. To elucidate the molecular basis of these features, we compared the RNA expression profile of the nucleus accumbens and prefrontal cortex of human brain from matched individual alcoholic and control cases using cDNA microarrays. Approximately 6% of genes with a marked alcohol response were common to the two brain regions. Alcohol-responsive genes were grouped into 11 functional categories. Predominant alcohol-responsive genes in the prefrontal cortex were those encoding DNA-binding proteins including transcription factors and repair proteins. There was also a down-regulation of genes encoding mitochondrial proteins, which could result in disrupted mitochondrial function and energy production leading to oxidative stress. Other alcohol-responsive genes in the prefrontal cortex were associated with neuroprotection/apoptosis. In contrast, in the nucleus accumbens, alcohol-responsive genes were associated with vesicle formation and regulation of cell architecture, which suggests a neuroadaptation to chronic alcohol exposure at the level of synaptic structure and function. Our data are in keeping with the previously reported alcoholism-related pathology characteristic of the prefrontal cortex, but suggest a persistent decrease in neurotransmission and changes in plasticity in the nucleus accumbens of the alcoholic.

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Section: Discussionmentioning

confidence: 93%

Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics

Flatscher-Bader

Brug

Hwang

et al. 2005

Journal of Neurochemistry

143

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“…Mitochondrial fractions from cultured mesencephalic neurons treated with CAP or AEA were prepared as described previously with some modifications (Rajgopal et al, 2003). Briefly, cells were homogenized with buffer containing 20 mM HEPES, pH 7.5, 250 mM sucrose, 10 mM KCl, 1.5 mM MgCl 2 , 1 mM EDTA, 1 mM EGTA, 1 mM DTT, 0.1 mM PMSF, and a protease inhibitor mixture.…”

Section: N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(24-dichlorophenyl)-4mentioning

confidence: 99%

Transient Receptor Potential Vanilloid Subtype 1 Mediates Cell Death of Mesencephalic Dopaminergic NeuronsIn VivoandIn Vitro

Kim¹,

Lee²,

Chung³

et al. 2005

J. Neurosci.

146

145

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“…In animal models, chronic alcohol treatment is associated with neuronal loss in hippocampal formation and basal forebrain [7]. Recent studies [8][9][10] have reported cytochrome c release [8,9], activation of m-calpain [9,10] after chronic ethanol treatment. Chronic alcohol administration leads to induction of apoptosis [8] mechanisms of cell death may differ.…”

Section: Introductionmentioning

confidence: 99%

Cell Death is Associated with Reduced Base Excision Repair During Chronic Alcohol Administration in Adult Rat Brain

2008

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The cell death cascades in different brain regions namely hippocampus and frontal cortex of rats fed with 10% (v/v) ethanol for 12 weeks, was examined. After Western blotting, different cell death associated proteins displayed differential activation in the two regions observed. In hippocampus, activated caspase-3 and caspase-7 resulted in subsequent cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). Cytochrome c release to cytosol and apoptosis inducing factor (AIF) translocation to nucleus was marginal. B-cell leukemia/lymphoma-2 (Bcl-2) translocation to cytosol was significant whereas Bcl-2-associated X protein (Bax) and Bcl-associated death protein (Bad) were largely located in cytosol. Further, upregulation of N-methyl D-aspartate receptor subunit 1 (NMDAR1), N-methyl D-aspartate receptor subunit 2B (NMDAR2B), N-methyl D-aspartate receptor subunit 2C (NMDAR2C) and activation of calpains were observed. In frontal cortex, caspase-3 activation, cleavage of PARP-1 and nuclear translocation of AIF were more pronounced. Moreover, cytochrome c release to cytosol, Bcl-2 translocation to cytosol was evident. However, levels of Bax, Bad, NMDA receptor subunits, and calpains were unaffected. Apoptosis was further substantiated by in situ staining for terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). Results of the current study revealed that frontal cortex exhibits a higher level of ethanol-induced apoptosis relative to hippocampus. DNA polymerase beta assay and immunoblot showed significant loss in base excision repair in ethanol treated group.

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Differential modulation of apoptosis-associated proteins by ethanol in rat cerebral cortex and cerebellum

Cited by 28 publications

References 34 publications

Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics

Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics

Transient Receptor Potential Vanilloid Subtype 1 Mediates Cell Death of Mesencephalic Dopaminergic NeuronsIn VivoandIn Vitro

Cell Death is Associated with Reduced Base Excision Repair During Chronic Alcohol Administration in Adult Rat Brain

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