关键词: AMPK/SIRT1 Nr1d1 PI3K/AKT PTEN and Bmal1 Senescence

Mesh : Male Animals Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism genetics ARNTL Transcription Factors / metabolism genetics Mice Physical Conditioning, Animal / physiology Mice, Inbred C57BL Apoptosis Aging / metabolism Prostate / metabolism pathology Up-Regulation Circadian Rhythm / physiology

来  源:   DOI:10.1016/j.lfs.2024.122800

Abstract:
BACKGROUND: Aging increases the prevalence of prostate cancer. The circadian clock coordinates metabolism, cell cycle, and tumor suppressor p53. Although physical exercise has several effects on preventing prostate diseases, its effect on regulating genes and proteins of the circadian rhythm of the prostate needs to be better evaluated. The present study verified expression of REV-ERBα (Nr1d1), Bmal1, apoptosis, tumor suppressors, energetic metabolism markers, and androgen receptors in the prostatic microenvironment in 18-month-old mice submitted to combined physical training.
METHODS: C57BL/6 J mice were divided into 2 groups: 6 months-old (n = 10) and 18 months-old, (n = 20). The 18-month-old animals were divided into 2 subgroups: sedentary (n = 10, 18 m Sed) and submitted to combined physical training (n = 10, 18 m TR). Combined physical training protocol was performed by running on the treadmill (40-60 % of incremental load test) and climbing strength training (40-50 % of maximum repetition test), consisting of 5×/week (3 days aerobic and 2 days strength) for 3 weeks. The prostate was prepared for Western blot and RT-qPCR analysis, and the plasm was prepared for the biochemistry analysis.
RESULTS: Combined physical exercise during aging led to increased levels of Bmal1 and decreased levels of REV-ERBα in the prostate. These results were accompanied by a reduction in the AMPK/SIRT1/PGC-1α proteins and an increase in the PI3K/AKT and p53/PTEN/caspase 3 pathways, promoting apoptotic potential.
CONCLUSIONS: These findings suggest that strength and aerobic physical exercise may be preventive in the development of preneoplastic molecular alterations and age-related features by re-synchronizes Bmal1 and REV-ERBα in prostatic tissues.
摘要:
背景:衰老会增加前列腺癌的患病率。生物钟协调新陈代谢,细胞周期,肿瘤抑制基因p53.尽管体育锻炼对预防前列腺疾病有多种作用,它对前列腺昼夜节律的基因和蛋白质的调节作用需要更好地评估。本研究验证了REV-ERBα(Nr1d1)的表达,Bmal1,凋亡,肿瘤抑制剂,能量代谢标记,接受联合体育锻炼的18个月大小鼠前列腺微环境中的雄激素受体。
方法:C57BL/6J小鼠分为2组:6月龄(n=10)和18月龄,(n=20)。将18个月大的动物分为2个亚组:久坐(n=10,18mSed)和接受联合体育锻炼(n=10,18mTR)。通过在跑步机上跑步(增量负荷测试的40-60%)和攀岩力量训练(最大重复测试的40-50%)进行组合体能训练方案,由5×/周(3天有氧和2天强度)组成,持续3周。准备前列腺进行Westernblot和RT-qPCR分析,并制备了用于生化分析的浆。
结果:衰老过程中的联合体育锻炼导致前列腺中Bmal1水平升高和REV-ERBα水平降低。这些结果伴随着AMPK/SIRT1/PGC-1α蛋白的减少和PI3K/AKT和p53/PTEN/caspase3途径的增加,促进凋亡潜能。
结论:这些研究结果表明,通过使前列腺组织中的Bmal1和REV-ERBα重新同步,力量和有氧体育锻炼可能在肿瘤前期分子改变和年龄相关特征的发展中具有预防性作用。
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