Alcohol-Related Brain Damage in Humans
Data(s) |
01/02/2016
01/02/2016
03/04/2014
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Resumo |
Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann's area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin beta II, and alpha- and beta-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in a-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in beta-spectrin protein levels, and a significant increase in transmembranous alpha 3 (catalytic) subunit of the Na+, K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of a-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic alpha-and beta-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics |
Identificador |
PLOS ONE 9(4) 2014 : (2014) // Article ID e93586 1932-6203 http://hdl.handle.net/10810/17169 10.1371/journal.pone.0093586 |
Idioma(s) |
eng |
Publicador |
Public Library Science |
Relação |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093586#abstract0 |
Direitos |
2014 Erdozain et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. info:eu-repo/semantics/openAccess |
Palavras-Chave | #l-isoaspartil methyltransferase #gene-expression #frontal-cortex #acetaldehyde adducts #NA+/K+-ATPase #rat-brain #ethanol #NA,K-ATPase #proteomics #tibulin |
Tipo |
info:eu-repo/semantics/article |