Modulation of gene expression of SMP-30 by LPS and calorie restriction during aging process
Modulation of gene expression of SMP-30 by LPS and calorie restriction during aging process
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DOI：
10.1016/j.exger.2004.04.005
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发表时间：
2004-08-01
影响因子：
3.9
通讯作者：
Chung, HY
中科院分区：
文献类型：
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作者：
Jung, KJ;Ishigami, A;Chung, HY
衰老标志物蛋白-30（SMP-30）被认为是一种重要的衰老标志物，目前已被鉴定为钙离子结合蛋白。已显示SMP-30通过增强质膜Ca 2+泵送活性来减弱由细胞内Ca 2+积累引起的细胞死亡。尽管有报道称，随着衰老，SMP-30会减少，但目前，这种减少的机制尚未完全明确，也没有广泛探索与SMP-30调节相关的机制。在目前的研究中，我们使用众所周知的卡路里限制（CR）范式的抗衰老作用来探索SMP-30基因表达的年龄相关变化。我们研究的重点是基于CR防御与年龄相关的氧化应激和炎症过程的能力。本研究使用6、12、18和24月龄Fischer 344大鼠的肾脏和肝脏。将大鼠分为两组，自由（AL）喂养和40%限制CR。结果显示，SMP-30的表达随着年龄的增长而下降，CR明显减弱了这种下降。为了将SMP-30基因表达与氧化状态之间的变化相关联，监测了衰老期间SMP-30表达和活性氧（ROS）的产生以及产生自由基的脂多糖（LPS）。我们的数据表明，SMP-30的下调伴随着ROS产生和LPS诱导的ROS增加。CR的强效抗衰老和抗氧化作用通过减少ROS有效抑制了与年龄相关的SMP-30下调。(C)2004年爱思唯尔公司All rights reserved.
Senescence marker protem-30 (SMP-30) has been proposed as an important aging marker and is now functionally identified as a Ca2+ binding protein. SMP-30 has been shown to blunt cell death caused by intracellular Ca2+ accumulation by enhancing plasma membrane Ca2+-pumping activity. Although SMP-30 is reported decrease during aging, at present, neither has the mechanism underlying this decrease been fully defined, nor have the mechanisms related to the modulation of SMP-30 been extensively explored. In the current study, we used the well-known anti-aging action of the calorie restriction (CR) paradigm to explore age-related changes in SMP-30 gene expression. The thrust of our investigation was based on CR's ability to defend against age-related oxidative stress and the inflammatory process. The kidney and liver from Fischer 344 rats at 6, 12, 18 and 24 months of age were utilized for this study. The rats were divided into two groups, ad libitum (AL)-fed and 40% restricted CR. Results showed that SMP-30 expression declined with age and that this decline was clearly blunted by CR. To correlate changes between SMP-30 gene expression and the oxidative status, SMP-30 expression and the production of reactive oxygen species (ROS) during aging and free-radical generating lipopolysaccharide (LPS) were monitored. Our data showed that the down-regulation of SMP-30 was accompanied by increased ROS generation and LPS-induced ROS. The potent anti-aging and anti-oxidative action of CR effectively suppressed the age-related down-regulation of SMP-30 by ROS reduction. (C) 2004 Elsevier Inc. All rights reserved.