Sirtuin 1 participates in the process of age-related retinal degeneration
Sirtuin 1 participates in the process of age-related retinal degeneration
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Sirtuin 1 参与年龄相关性视网膜变性的过程。
DOI：
10.1016/j.bbrc.2015.10.139
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发表时间：
2015-12-04
影响因子：
3.1
通讯作者：
Yang, Ke
中科院分区：
文献类型：
--
作者：
Zeng, Ying;Yang, Ke
背景：衰老过程涉及视网膜细胞损伤，导致视觉功能障碍。Sirtuin（Sirt）1可以防止氧化应激、DNA损伤和细胞凋亡。在本研究中，我们测量了Sirt 1作为一个功能调节器在视网膜中的表达在老化process.Methods：在年轻（1个月）和老年（19个月）Sprague-Dawley（SD）大鼠的视觉功能和Sirt 1表达。进行视网膜电图（ERG）和实时聚合酶链反应（PCR）或Western印迹。将Sirt 1的激活剂白藜芦醇以5 mg/kg/d的剂量口服给SD大鼠19个月。Sirt 1、脑源性神经营养因子（BDNF）和原肌球蛋白受体激酶B（Trk B）的表达在接受和未接受白藜芦醇治疗的小鼠视网膜中进行了评估。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测细胞凋亡。结果：随着b波振幅的降低，Sirt 1在老年视网膜中的表达水平明显低于年轻视网膜。白藜芦醇治疗19个月后，Sirt 1表达水平和b波振幅增加。白藜芦醇处理的老年大鼠，BDNF和TrkB的表达水平上调。与年轻的视网膜相比，老年人的视网膜表现出更高的凋亡，但白藜芦醇延迟了这一进程。结论：我们的数据表明，减少Sirt 1的表达在视网膜的老化过程中，但增强Sirt 1的表达逆转了视网膜的变性。提示Sirt 1表达上调可能通过调节神经营养因子及其受体对视网膜神经元和视功能产生保护作用。(C)2015 Elsevier Inc. All rights reserved.
Background: The process of aging involves retinal cell damage that leads to visual dysfunction. Sirtuin (Sirt) 1 can prevent oxidative stress, DNA damage, and apoptosis. In the present study, we measured the expression of Sirt1 as a functional regulator in the retina during the aging process.Methods: The visual function and Sirt1 expression in young (1 month) and old (19 months) Sprague-Dawley (SD) rats. Electroretinogram (ERG) and real-time polymerase chain reaction (PCR) or Western blotting were performed. Resveratrol, an activator of Sirt1, was orally administered to SD rats at a dose of 5 mg/kg/day for 19 months. The expression of Sirt1, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) was evaluated in the retinas of mice that did and did not receive resveratrol treatment. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.Results: With decreasing b-wave amplitude, the expression level of Sirt1 was significantly reduced in aged retinas compared to that in young retinas. After 19 months of treatment with resveratrol, the Sirt1 expression level and b-wave amplitude increased. In old rats treated with resveratrol, the expression levels of BDNF and TrkB were up-regulated. Compared to young retinas, the aged retinas exhibited higher apoptosis, but resveratrol delayed this process.Conclusions: Our data demonstrated a reduction of Sirt1 expression during the aging process of the retina, but enhancing Sirt1 expression reversed the degeneration of the retina. These results suggested that increasing Sirt1 expression may protect retinal neurons and visual function via regulating neurotrophin and its receptor. (C) 2015 Elsevier Inc. All rights reserved.