Choi Hee-Soo, Ahn Ji Hyeon, Park Joon Ha, Won Moo-Ho, Lee Choong-Hyun
Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, South Chungcheong 31116, Republic of Korea.
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea.
Mol Med Rep. 2016 Mar;13(3):2409-14. doi: 10.3892/mmr.2016.4835. Epub 2016 Jan 29.
Redd1, also known as RTP801/Dig2/DDIT4, is a stress-induced protein and a negative regulator of mammalian target of rapamycin (mTOR). Redd1 is also closely associated with oxidative stress and DNA damage. In the present study, age‑related changes in the protein expression levels of mTOR and Redd1 were investigated using immunohistochemistry and western blot in the gerbil hippocampus at postnatal month (PM) 3, 6, 12 and 24. No significant differences were identified in the levels of mTOR among the experimental groups, whereas, the levels of phosphorylated mTOR decreased with age. The protein expression levels of Redd1 were observed to gradually increase with age; in the PM 24 group, the level was significantly increased (~189.2%), compared with the PM 3 group. In addition, Redd1 immunoreactivity was significantly increased in the hippocampal principal neurons of the PM 24 group, including the pyramidal cells in the hippocampus proper and granule cells in the dentate gyrus, compared with the other experimental groups. These results demonstrated that the protein expression of Redd1 in the hippocampus was markedly increased during normal aging, indicating that the age-related increase in the expression of Redd1 may be closely associated with age-related hippocampal change.
Redd1,也被称为RTP801/Dig2/DDIT4,是一种应激诱导蛋白,也是雷帕霉素哺乳动物靶标(mTOR)的负调节因子。Redd1还与氧化应激和DNA损伤密切相关。在本研究中,使用免疫组织化学和蛋白质印迹法,对出生后3、6、12和24个月沙鼠海马中mTOR和Redd1蛋白表达水平的年龄相关变化进行了研究。各实验组间mTOR水平未发现显著差异,而磷酸化mTOR水平随年龄下降。观察到Redd1蛋白表达水平随年龄逐渐升高;与出生后3个月组相比,出生后24个月组的水平显著升高(约189.2%)。此外,与其他实验组相比,出生后24个月组海马主要神经元(包括海马体中的锥体细胞和齿状回中的颗粒细胞)中的Redd1免疫反应性显著增加。这些结果表明,在正常衰老过程中,海马中Redd1的蛋白表达显著增加,表明Redd1表达的年龄相关增加可能与年龄相关的海马变化密切相关。