Poly(ADP-ribose) polymerase activity in intact or permeabilized leukocytes from mammalian species of different longevity.
Poly(ADP-ribosyl)ation is a eukaryotic posttranslational protein modification catalyzed by poly(ADP-ribose) polymerase (PARP), a highly conserved nuclear enzyme which uses NAD as substrate. We have previously tested PARP activity in permeabilized mononuclear blood cells (MNC) from 13 mammalian species as a function of the species-specific life span. A direct and maximal stimulus of PARP activation was provided by including saturating amounts of a double-stranded oligonucleotide in the PARP-reaction buffer. The data yielded a strong positive correlation between PARP activities and the species' maximal life spans (r = 0.84; p << 0.001). Here, we investigated the formation of poly(ADP-ribose) in living MNC from two mammalian species with widely differing longevity (rat and man) by immunofluorescence detection of poly(ADP-ribose). The fraction of positive cells was recorded, following gamma-irradiation of intact MNC, as a semiquantitative estimation of poly(ADP-ribose) formation. Human samples displayed a significantly higher percentage of positivity than did those from rats, consistent with our previous results on permeabilized cells. While rat MNC had a higher NAD content than human MNC, the number of radiation-induced DNA strand breaks was not significantly different in the two species. Since poly(ADP-ribosyl)ation is apparently involved in DNA repair and the cellular recovery from DNA damage, we speculate that the higher poly(ADP-ribosyl)ation capacity of long-lived species might more efficiently help to slow down the accumulation of unrepaired DNA damage and of genetic alterations, as compared with short-lived species.
Bürkle
A
A
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Heidelberg, Germany.
Müller
M
M
Wolf
I
I
Küpper
J H
JH
D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008136:Longevity; D011065:Poly(ADP-ribose) Polymerases / Q000097:blood*; D051381:Rats / Q000378:metabolism*; D013045:Species Specificity
D011065:Poly(ADP-ribose) Polymerases