Cellular environment facilitates protein accumulation in aged rat hippocampus

Aging represents the main risk factor to develop Alzheimer disease (AD) and protein aggregation constitutes a pathological hallmark thought to be involved in the etiology of this disease. Here, we show that, in basal conditions, the expression of chaperones calnexin, protein disulfide isomerase (PDI...

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Bibliographic Details
Published in:Neurobiology of aging 2006-07, Vol.27 (7), p.973-982
Main Authors: Paz Gavilán, M., Vela, José, Castaño, Angélica, Ramos, Blanca, del Río, Juan C., Vitorica, Javier, Ruano, Diego
Format: Article
Language:English
Subjects:
Aging
Aging - metabolism
Aging - pathology
Alzheimer Disease - metabolism
Alzheimer Disease - physiopathology
Animals
Apoptosis - physiology
Calnexin - metabolism
Cellular stress
Heat-Shock Proteins - metabolism
Hippocampus
Hippocampus - metabolism
Hippocampus - pathology
Male
Molecular chaperones
Molecular Chaperones - metabolism
Nerve Tissue Proteins - metabolism
Neurons - metabolism
Neurons - pathology
Proteasome
Proteasome Endopeptidase Complex - metabolism
Protein accumulation
Protein Disulfide-Isomerases - metabolism
Protein Folding
Rats
Signal Transduction - physiology
Stress, Physiological - metabolism
Stress, Physiological - physiopathology
Transcription Factor CHOP - metabolism
Ubiquitin - metabolism
Up-Regulation - physiology
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Summary:Aging represents the main risk factor to develop Alzheimer disease (AD) and protein aggregation constitutes a pathological hallmark thought to be involved in the etiology of this disease. Here, we show that, in basal conditions, the expression of chaperones calnexin, protein disulfide isomerase (PDI) and Grp78 was decreased in aged hippocampus, whereas the protein ubiquitination increased, suggesting the existence of age-related deficits in the systems involved in the defense against unfolded proteins. Interestingly, when cellular stress was induced by intra-hippocampal lactacystin injection, the aged rats were less efficient than young animals in alleviating the protein accumulation and, as an important factor, did not induce the expression of chaperones as young animals. However, the expression of the pro-apoptotic factor CHOP/GADD153 was induced and caspase-12 was activated in stressed aged rats but not in young animals. Current results demonstrated that unfolding protein response (UPR) is not correctly activated in aged rat hippocampus. Consequently, the up-regulation of apoptotic pathway mediators is increased in aged rats. Results might provide further understanding of the pathogenic mechanisms of age-related neurodegenerative disorders.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2005.05.010