Journal of neurochemistry, 2009, Vol.108 (1), p.260-272
2009
Details
- Autor(en) / Beteiligte
- Titel
- Age-related increase in the immunoproteasome content in rat hippocampus: molecular and functional aspects
- Ist Teil von
- Journal of neurochemistry, 2009, Vol.108 (1), p.260-272
- Ort / Verlag
- Oxford, UK: Oxford, UK : Blackwell Publishing Ltd
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Alma/SFX Local Collection
- Beschreibungen/Notizen
- Alterations in the proteasome activity in the CNS have been described during aging. However, a detailed study of all proteasome subunits is actually lacking. We have analyzed, in vivo, the age-related modifications in the molecular composition of hippocampal proteasomes. We found that the immunoproteasome/proteasome ratio was increased in aged hippocampus. The processing of the low-molecular-mass protein (LMP)7/β₅i subunit, practically absent in young hippocampus, was increased in aged animals. Among the potential factors underlying these modifications we evaluated the neuroinflammation and the transcription factor Zif268. Lipopolysaccharide (LPS)-induced neuroinflammation in young rats, up-regulated the expression of immunoproteasome subunits and increased the processing of the LMP7/β₅i protein. Moreover, the hydrophobicity of cellular peptides, analyzed by liquid chromatography, increased in both, young LPS-injected animals and aged rats, suggesting that immunoproteasomes including the LMP7/β₅i subunit could, at least in part, account for this modification. Also, the mRNA expression of the transcription factor Zif268, which down-regulates the immunoproteasome subunit LMP7/β₅i by binding to sequences within the promoter regions, was decreased in both, aged hippocampus and young LPS-injected animals. Finally, we found that spatial memory training in young animals, a situation in which the expression of Zif268 is increased, modified the mRNA expression of the constitutive and catalytic subunits in an opposite manner. Based on present data, we propose that the age-related increases in the content of hippocampal immunoproteasome is mostly because of neuroinflammatory processes associated to aging.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-3042eISSN: 1471-4159DOI: 10.1111/j.1471-4159.2008.05762.xTitel-ID: cdi_proquest_miscellaneous_66749683
- Format
- –
- Schlagworte
- Aging, Aging - metabolism, Animals, Biochemistry, Biological and medical sciences, Central nervous system, Central neurotransmission. Neuromudulation. Pathways and receptors, Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases, Early Growth Response Protein 1 - genetics, Early Growth Response Protein 1 - metabolism, Fundamental and applied biological sciences. Psychology, Gene Expression Regulation - drug effects, Gene Expression Regulation - physiology, hippocampal formation, hippocampus, Hippocampus - drug effects, Hippocampus - metabolism, Hippocampus - ultrastructure, Immunoglobulins - metabolism, immunoproteasome, Lipopolysaccharides - pharmacology, Male, Maze Learning - physiology, Medical sciences, Molecular biology, Multienzyme Complexes - chemistry, Multienzyme Complexes - genetics, Multienzyme Complexes - metabolism, neurodegeneration, neuroinflammation, Neurology, proteasome, proteasome endopeptidase complex, Proteasome Endopeptidase Complex - chemistry, Proteasome Endopeptidase Complex - genetics, Proteasome Endopeptidase Complex - metabolism, Protein Subunits - genetics, Protein Subunits - metabolism, Rats, Rats, Wistar, RNA, Messenger - metabolism, Rodents, Subcellular Fractions - metabolism, Vertebrates: nervous system and sense organs