APE/Ref-1 responses to oxidative stress in aged rats.
Chronic oxidative stress has been hypothesized to be a major contributor to the aging process. The continued exposure to reactive oxygen species (ROS) generated by oxidative metabolism or environmental sources can damage critical cellular structures and be responsible for some age-related pathology. The exposure of rodents to 100% oxygen, isobaric hyperoxia, increases ambient ROS levels and significantly increases apoptosis in brain. The deleterious effects of ROS also include increased lipid peroxidation, protein oxidation, and DNA damage. Although differences in the relative amounts of oxidative stress in young and old brains have been observed, the mechanisms responsible for impaired aging-associated DNA repair processes have not been characterized. We measured DNA levels of the DNA repair enzyme apurinic/apyrimidinic endonuclease (APE/Ref-1) protein by Western blot analysis in the brains of young (3-month) and old (30-month) male rats exposed to isobaric hyperoxia. Given that APE/Ref-1 is the rate-limiting enzyme in the repair pathway of apurinic/apyrimidinic sites generated in DNA by oxidative damage, we assumed that APE/Ref-1 protein levels were a good reflection of ongoing DNA base excision repair. Isobaric hyperoxia stimulated APE/Ref-1 expression in the hippocampus and basal forebrain of young rats experiencing 100% oxygen for 6 hr, while aged rats showed no significant changes in APE/Ref-1 protein levels in all brain areas at any time tested (0-48 hr) after hyperoxia. Differences in the stress-induced levels of expression of DNA repair enzymes may contribute to apoptotic increases and pathology associated with the aging process.
Edwards
M
M
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, USA.
Rassin
D K
DK
Izumi
T
T
Mitra
S
S
Perez-Polo
J R
JR
D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D019757:Carbon-Oxygen Lyases / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000032:analysis; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004790:Enzyme Induction; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity*; D016548:Prosencephalon / Q000201:enzymology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species
D017382:Reactive Oxygen Species; D004247:DNA; D019757:Carbon-Oxygen Lyases; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D010100:Oxygen