Biotechnology and Molecular Medicine, A.I. Virtanen Institute, Biocenter Kuopio, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, 70211, Kuopio, Finland.
Transgenic Res. 2011 Apr;20(2):387-96. doi: 10.1007/s11248-010-9422-5. Epub 2010 Jun 25.
Enhanced polyamine catabolism via polyamine acetylation-oxidation elevates the oxidative stress in an organism due to increased production of reactive oxygen species (ROS). We studied a transgenic mouse line overexpressing the rate limiting enzyme in the polyamine catabolism, spermidine/spermine N (1)-acetyltransferase (SSAT) that is characterized by increased putrescine and decreased spermidine and spermine pools. In order to protect the mice from the chronic oxidative stress produced by the activation of polyamine catabolism, the hepatic expression of the transcription factor p53 was found threefold elevated in the transgenic mice. In addition, the prolonged activation of p53 accelerated the aging of transgenic mice and reduced their lifespan (50%). Aging was associated with decreased antioxidant enzyme activities. In the transgenic mice the activities of catalase and Cu, Zn-superoxide dismutase (SOD) were 42 and 23% reduced respectively, while the expression of CYP450 2E1 was 60% decreased and oxidative stress measured as protein carbonyl content was tenfold elevated. In the transgenic mice, the age-related repression of the different antioxidant enzymes served as a protection against the hepatotoxic effects of carbon tetrachloride and thioacetamide.
通过多胺乙酰化-氧化增强多胺分解代谢会增加活性氧物种 (ROS) 的产生，从而增加生物体的氧化应激。我们研究了一种过表达多胺分解代谢限速酶精脒/精胺 N(1)-乙酰转移酶 (SSAT) 的转基因小鼠品系，其特点是腐胺增加，精脒和精胺减少。为了防止由于多胺分解代谢的激活而产生的慢性氧化应激对小鼠造成损害，我们发现转基因小鼠中转录因子 p53 的肝表达增加了三倍。此外，p53 的长期激活加速了转基因小鼠的衰老并使其寿命缩短（50%）。衰老与抗氧化酶活性降低有关。在转基因小鼠中，过氧化氢酶和 Cu、Zn-超氧化物歧化酶 (SOD) 的活性分别降低了 42%和 23%，而 CYP450 2E1 的表达降低了 60%，并且蛋白质羰基含量的氧化应激增加了十倍。在转基因小鼠中，不同抗氧化酶的年龄相关抑制作用可作为对四氯化碳和硫代乙酰胺肝毒性作用的保护。
