Effect of caloric restriction on base-excision repair (BER) in the aging rat brain.
Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was approximately 1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase beta and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE.
Kisby
Glen E
GE
Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, OR 97239, USA. kisby@ohsu.edu
Kohama
Steven G
SG
Olivas
Antoinette
A
Churchwell
Mona
M
Doerge
Daniel
D
Spangler
Edward
E
de Cabo
Rafael
R
Ingram
Donald K
DK
Imhof
Barry
B
Bao
Gaobin
G
Kow
Yoke W
YW
D000368:Aged; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D031204:Caloric Restriction; D004249:DNA Damage; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase