山东医药2017,Vol.57Issue(42):25-28,4.DOI:10.3969/j.issn.1002-266X.2017.42.007
雷帕霉素对衰老细胞生物节律关键基因的调控作用观察
Regulatory effect of rapamycin on key genes of circadian rhythm in senescent cells
摘要
Abstract
Objective To investigated the effect of rapamycin on the cell autonomous circadian rhythm of senescent cells. Methods We induced replicative senescence of human dermal fibroblasts by series passage. The senescent human dermal fibroblasts cells were identified by SA-β-gal staining. The senescent human dermal fibroblasts cells were synchro-nized by 50% horse serum,and treated with DMSO or 200 nmol/L rapamycin. The oscillation profiles of BMAL1,PER2, CRY1,Rev-erbα and Rorα were examined by fluorogenic quantitative PCR. The circadian rhythm of genes was analyzed by JTK-CYCLE software. The protein expression of BMA1,CRY1,and PER2 was detected by Western blotting. Results The mRNA expression of PER2,CRY1,Rev-erbα and Rorα in the observation group was higher than that of the control group (all P <0.05). The biorhythm cycle of BMAL1,CRY1,Rev-erbα,and Rorα genes in the control group was 24 h, and the biorhythm cycle of PER2 gene was 28 h. The biorhythm cycle of BMAL1,CRY1,and Rorα genes in the observa-tion group was 24 h,and the biorhythm cycle of Rev-erbα gene was 27.5h. The expression of CRY1 protein in the obser-vation group was significantly higher than that in the control group,while PER2 protein expression was significantly lower than that in the control group (both P < 0.05). No significant difference was found in BMAL1 mRNA and protein expres-sion between these two groups. Conclusion Rapamycin can increase the expression of BMAL1,PER2,CRY1,Rev-erbαand Rorα mRNA in the aging human dermal fibroblasts and shorten the rhythmic cycle of PER2,which plays a regulatory role in the disturbance of circadian clock function.关键词
生物节律/雷帕霉素/生物节律关键基因/芳烃受体核转位蛋白3/节律周期蛋白2/蓝光受体蛋白1/孤儿核受体α/孤核受体α/哺乳动物雷帕霉素靶蛋白Key words
biorhythm/rapamycin/key gene of biorhythm/aryl hydrocarbon receptor nuclear translocator 3/PER2/cryptochrome 1/orphan nuclear receptor α/orphan nuclear receptor α/mammalian target of rapamycin分类
生物科学引用本文复制引用
刘佐君,刘宝华,孟凡彪..雷帕霉素对衰老细胞生物节律关键基因的调控作用观察[J].山东医药,2017,57(42):25-28,4.基金项目
国家自然科学基金资助项目(81601215). (81601215)