Document Detail


Misregulation of poly(ADP-ribose) polymerase-1 activity and cell type-specific loss of poly(ADP-ribose) synthesis in the cerebellum of aged rats.
MedLine Citation:
PMID:  15857403     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Protein modification by ADP-ribose polymers is a common regulatory mechanism in eukaryotic cells and is involved in several aspects of brain physiology and physiopathology, including neurotransmission, memory formation, neurotoxicity, ageing and age-associated diseases. Here we show age-related misregulation of poly(ADP-ribose) synthesis in rat cerebellum as revealed by: (i) reduced poly(ADP-ribose) polymerase-1 (PARP-1) activation in response to enzymatic DNA cleavage, (ii) altered protein poly(ADP-ribosyl)ation profiles in isolated nuclei, and (iii) cell type-specific loss of poly(ADP-ribosyl)ation capacity in granule cell layer and Purkinje cells in vivo. In particular, although PARP-1 could be detected in virtually all granule cells, only a fraction of them appeared to be actively engaged in poly(ADP-ribose) synthesis and this fraction was reduced in old rat cerebellum. NAD(+), quantified in tissue homogenates, was essentially the same in the cerebellum of young and old rats suggesting that in vivo factors other than PARP-1 content and/or NAD(+) levels may be responsible for the age-associated lowering of poly(ADP-ribose) synthesis. Moreover, PARP-1 expression was substantially down-regulated in Purkinje cells of senescent rats.
Authors:
M Malanga; M Romano; A Ferone; A Petrella; G Monti; R Jones; E Limatola; B Farina
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  93     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-28     Completed Date:  2005-07-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1000-9     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University Federico II, Naples, Italy. malanga@vetpharm.unizh.ch
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MeSH Terms
Descriptor/Qualifier:
Aging / metabolism*
Animals
Blotting, Western / methods
Brain / cytology,  enzymology*,  growth & development
Brain Chemistry / physiology
Cell Nucleus / enzymology
Immunohistochemistry / methods
Male
NAD / metabolism
Poly Adenosine Diphosphate Ribose / metabolism*
Poly(ADP-ribose) Polymerases / metabolism*
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
26656-46-2/Poly Adenosine Diphosphate Ribose; 53-84-9/NAD; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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