Misregulation of poly(ADP-ribose) polymerase-1 activity and cell type-specific loss of poly(ADP-ribose) synthesis in the cerebellum of aged rats.
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.
Malanga
M
M
Department of Biochemistry, University Federico II, Naples, Italy. malanga@vetpharm.unizh.ch
Romano
M
M
Ferone
A
A
Petrella
A
A
Monti
G
G
Jones
R
R
Limatola
E
E
Farina
B
B
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D001923:Brain Chemistry / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009243:NAD / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases