Son Tae Gen, Zou Yani, Jung Kyung Jin, Yu Byung Pal, Ishigami Akihito, Maruyama Naoki, Lee Jaewon
Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan, South Korea.
Mech Ageing Dev. 2006 May;127(5):451-7. doi: 10.1016/j.mad.2006.01.005. Epub 2006 Feb 28.
Senescence marker protein 30 (SMP30), an important aging marker molecule, has been identified functionally as a calcium regulatory protein. Recent evidence showed its new assumed role as an effective anti-oxidative property. However, the role of SMP30 in the brain has not been explored. To delineate its role in the brain, we utilized SMP30 knock-out (SMP30 KO) mice in the current study. We focused on the oxidative status of the brain by examining selected oxidative markers in brains of SMP30 KO mice. Results showed that the generation of reactive species (RS) and NADPH oxidase activities were significantly elevated in SMP30 deficient brain. The increased oxidative status in these mice was further confirmed by increased oxidatively modified proteins such as dityrosine formation and carbonylation in the cortex of SMP30 KO mice. Moreover, SMP30 deficient brain showed the increased Mac-1 protein and myeloperoxidase (MPO) activity in the brain, supporting the putative anti-oxidative action of SMP30. Interestingly, the activities of major antioxidant enzymes, superoxide dismutase, catalase and reduced glutathione peroxidase in the brain were not affected by SMP30 depletion. Our results documented that brain SMP30 has a protective action against oxidative damage, without influencing antioxidant enzyme status.
衰老标记蛋白30（SMP30）是一种重要的衰老标记分子，在功能上已被确定为一种钙调节蛋白。最近的证据表明它具有新的假定作用，即具有有效的抗氧化特性。然而，SMP30在大脑中的作用尚未得到探索。为了阐明其在大脑中的作用，我们在当前研究中使用了SMP30基因敲除（SMP30 KO）小鼠。我们通过检测SMP30 KO小鼠大脑中的选定氧化标记物，重点研究了大脑的氧化状态。结果表明，在SMP30缺陷型大脑中，活性物质（RS）的生成和NADPH氧化酶活性显著升高。SMP30 KO小鼠皮质中氧化修饰蛋白（如二酪氨酸形成和羰基化）的增加进一步证实了这些小鼠氧化状态的升高。此外，SMP30缺陷型大脑显示大脑中Mac-1蛋白和髓过氧化物酶（MPO）活性增加，支持了SMP30假定的抗氧化作用。有趣的是，大脑中主要抗氧化酶超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽过氧化物酶的活性不受SMP30缺失的影响。我们的结果证明，大脑中的SMP30对氧化损伤具有保护作用，而不影响抗氧化酶的状态。
