Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Exp Gerontol. 2013 Nov;48(11):1212-7. doi: 10.1016/j.exger.2013.04.010. Epub 2013 May 3.
Sirtuins (Sirt1-7) are nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases/ADP-ribosyltransferases that modulate many metabolic responses affecting aging. Sirtuins expressed in tissues and organs involved in systemic metabolism have been extensively studied. However, the characteristics of sirtuins in the retina, where local energy expenditure changes dynamically in response to light stimuli, are largely unknown. Here we analyzed sirtuin mRNA levels by real-time PCR, and found that all seven sirtuins are highly expressed in the retina compared with other tissues, such as liver. We then analyzed the sirtuin mRNA profiles in the retina over time, under a 12-h light/12-h dark cycle (LD condition) and in constant darkness (DD condition). All seven sirtuins showed significant daily variation under the LD condition, with all except Sirt6 being increased in the dark phase. The expression patterns were different under the DD condition, suggesting that sirtuin mRNA levels except Sirt6 are affected by light-dark condition. These findings were not obtained in the brain and liver. In addition, the mRNA expression patterns of Nicotinamide phosphoribosyltransferase (Nampt), peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and transcription factor A, mitochondrial (Tfam) in the retina, were similar to those of the sirtuins except Sirt6. Our observations provide new insights into the metabolic mechanisms of the retina and the sirtuins' regulatory systems.
Sirtuins (Sirt1-7) 是烟酰胺腺嘌呤二核苷酸 (NAD)-依赖性蛋白去乙酰化酶/ADP-核糖基转移酶,可调节影响衰老的许多代谢反应。在参与全身代谢的组织和器官中表达的 Sirtuins 已经得到了广泛的研究。然而,在视网膜中,局部能量消耗会根据光刺激动态变化,而 Sirtuins 的特征在很大程度上尚不清楚。在这里,我们通过实时 PCR 分析了 Sirtuin mRNA 水平,发现与其他组织(如肝脏)相比,所有 7 种 Sirtuins 在视网膜中均高度表达。然后,我们分析了在 12 小时光照/12 小时黑暗循环(LD 条件)和持续黑暗(DD 条件)下,视网膜中 Sirtuin mRNA 随时间的变化。在 LD 条件下,所有 7 种 Sirtuins 均表现出明显的日变化,除 Sirt6 外,所有 Sirtuins 在黑暗期均增加。在 DD 条件下的表达模式不同,表明除 Sirt6 外,Sirtuin mRNA 水平受到光暗条件的影响。这些发现并未在大脑和肝脏中获得。此外,视网膜中烟酰胺磷酸核糖基转移酶 (Nampt)、过氧化物酶体增殖物激活受体γ共激活因子 (PGC1α) 和转录因子 A、线粒体 (Tfam) 的 mRNA 表达模式与除 Sirt6 外的 Sirtuins 相似。我们的观察结果为视网膜的代谢机制和 Sirtuins 的调节系统提供了新的见解。