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Misregulation of poly(ADP‐ribose) polymerase‐1 activity and cell type‐specific loss of poly(ADP‐ribose) synthesis in the cerebellum of aged rats
Author(s) -
Malanga M.,
Romano M.,
Ferone A.,
Petrella A.,
Monti G.,
Jones R.,
Limatola E.,
Farina B.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03082.x
Subject(s) - poly adp ribose polymerase , nad+ kinase , cerebellum , ribose , biology , biochemistry , polymerase , microbiology and biotechnology , enzyme , endocrinology
Abstract 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.