Edwards M, Rassin D K, Izumi T, Mitra S, Perez-Polo J R
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, USA.
J Neurosci Res. 1998 Dec 1;54(5):635-8. doi: 10.1002/(SICI)1097-4547(19981201)54:5<635::AID-JNR8>3.0.CO;2-H.
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.
慢性氧化应激被认为是衰老过程的主要促成因素。持续暴露于氧化代谢或环境源产生的活性氧（ROS）会损害关键的细胞结构，并导致一些与年龄相关的病理变化。将啮齿动物暴露于100%氧气（等压高氧环境）会增加周围ROS水平，并显著增加大脑中的细胞凋亡。ROS的有害影响还包括脂质过氧化增加、蛋白质氧化和DNA损伤。尽管已观察到年轻和老年大脑中氧化应激相对量的差异，但与衰老相关的DNA修复过程受损的机制尚未明确。我们通过蛋白质印迹分析测量了暴露于等压高氧环境的年轻（3个月）和老年（30个月）雄性大鼠大脑中DNA修复酶脱嘌呤/脱嘧啶内切酶（APE/Ref-1）蛋白的DNA水平。鉴于APE/Ref-1是DNA氧化损伤产生的脱嘌呤/脱嘧啶位点修复途径中的限速酶，我们认为APE/Ref-1蛋白水平很好地反映了正在进行的DNA碱基切除修复。等压高氧刺激了暴露于100%氧气6小时的年轻大鼠海马体和基底前脑中APE/Ref-1的表达，而老年大鼠在高氧后的任何测试时间（0 - 48小时），所有脑区的APE/Ref-1蛋白水平均无显著变化。应激诱导的DNA修复酶表达水平差异可能导致细胞凋亡增加以及与衰老过程相关的病理变化。
