Effect of aging on intracellular distribution of abasic (AP) endonuclease 1 in the mouse liver.
The abasic (AP) endonuclease (APE1) plays a central role in the base excision repair (BER) pathway for repairing oxidatively damaged bases and abasic sites in mammalian genomes. We have investigated age-dependent changes in APE activity, contributed primarily by APE1, in total extracts as well as in nuclear, mitochondrial, and cytoplasmic compartments of mouse hepatocytes. The APE1 protein and mRNA levels did not differ significantly between the livers of 4-mo (young), 10-mo (middle-aged), and 20-mo (old) mice, and corresponds with similar APE activity. However, we observed a 2-fold increase in specific activity of APE1 in the nucleus, a 2-fold decrease in the cytoplasm, and a 6-fold increase in the mitochondrial matrix of hepatocytes of the old relative to the young animals. Surprisingly, in the middle-age animals we observed 30% increase in APE activity in the nucleus but 6-fold in the mitochondrial matrix. These results indicate age-dependent accumulation of APE1 in the nucleus and mitochondria. Such redistribution occurred early in the mitochondria during the aging process and preferential accumulation of APE in the nucleus was more gradual which may reflect distinct levels of oxidative stress in these organelles.
Szczesny
Bartosz
B
University of Texas Medical Branch, Sealy Center for Molecular Science, Department of Human Biological Chemistry and Genetics, Galveston, TX 77555, USA.
Mitra
Sankar
S
D000375:Aging / Q000378:metabolism*; D000818:Animals; D022082:Cellular Structures / Q000201:enzymology*; D003850:Deoxyribonuclease I / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000502:physiology
D003850:Deoxyribonuclease I