Sung Bokyung, Park Seongjoon, Ha Young Mi, Kim Dae Hyun, Park Chan Hum, Jung Kyung Jin, Kim Min Sun, Kim You Jung, Kim Mi Kyung, Moon Jeon-Ok, Yokozawa Takako, Kim Nam Deuk, Yu Byung Pal, Chung Hae Young
Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan, Korea.
Geriatr Gerontol Int. 2015 Feb;15(2):211-9. doi: 10.1111/ggi.12255. Epub 2014 Aug 27.
Many intracellular components have been implicated in the regulation of redox homeostasis, but homeostasis can be unbalanced by reactive species (RS), which also probably contribute to underlying inflammatory processes. Nuclear factor-κB (NF-κB) is a well-known redox-sensitive transcription factor that controls the genes responsible for regulating inflammation.
In the present study, the authors investigated the effect of short-term salicylideneamino-2-thiophenol (SAL-2) administration on the modulation of pro-inflammatory NF-κB through redox regulation in aged rats. In addition, we compared the effects of SAL-2 and caloric restriction (CR) on inflammation and redox balance. The subjects were 24-month-old (old) Fischer 344 rats administered SAL-2 (10 mg/kg/day) by dietary supplementation or placed on a 30% restricted diet for 10 days, and 6-month-old (young) rats fed ad libitum for 10 days.
We found that NF-κB activation and the expressions of its related genes (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, cyclooxygenase-2 and inducible nitric oxide synthase) were suppressed by SAL-2 supplementation in old CR rats to the levels observed in young rats. In addition, our molecular studies showed that the inhibitory effect of SAL-2 on the activation of NF-κB was mediated by the ability of SAL-2 to block the nuclear translocations of cytosolic thioredoxin and redox factor-1.
These findings strongly indicate that SAL-2 stabilizes age-related redox imbalance and modulates the signal transduction pathway involved in the age-associated molecular inflammatory process.
许多细胞内成分都与氧化还原稳态的调节有关，但活性物质（RS）可能会破坏这种稳态，而活性物质也可能参与潜在的炎症过程。核因子-κB（NF-κB）是一种众所周知的对氧化还原敏感的转录因子，它控制着负责调节炎症的基因。
在本研究中，作者研究了短期给予水杨叉氨基-2-硫酚（SAL-2）对老年大鼠通过氧化还原调节来调控促炎NF-κB的作用。此外，我们比较了SAL-2和热量限制（CR）对炎症和氧化还原平衡的影响。实验对象为24月龄（老年）的Fischer 344大鼠，通过饮食补充给予SAL-2（10毫克/千克/天），或进行10天的30%热量限制饮食，以及6月龄（年轻）大鼠自由进食10天。
我们发现，在老年热量限制大鼠中，补充SAL-2可将NF-κB的激活及其相关基因（血管细胞黏附分子-1、细胞间黏附分子-1、环氧化酶-2和诱导型一氧化氮合酶）的表达抑制至年轻大鼠的水平。此外，我们的分子研究表明，SAL-2对NF-κB激活的抑制作用是通过其阻断胞质硫氧还蛋白和氧化还原因子-1核转位的能力介导的。
这些发现有力地表明，SAL-2可稳定与年龄相关的氧化还原失衡，并调节与年龄相关的分子炎症过程中涉及的信号转导途径。
