Combined physical exercise re-synchronizes expression of Bmal1 and REV-ERBα and up-regulates apoptosis and metabolism in the prostate during aging.

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. CONCLUSION: 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.

Long exposure to a mixture of endocrine disruptors prediposes the ventral prostate of rats to preneoplastic lesions.

Endocrine disruptors (ED) are compounds dispersed in the environment that modify hormone biosynthesis, affecting hormone-dependent organs such as the prostate. Studies have only focused on evaluating the effects of ED alone or in small groups and short intervals and have not adequately portrayed human exposure. Therefore, we characterized the prostate histoarchitecture of rats exposed to an ED mixture (ED Mix) mimicking human exposure. Pregnant females of the Sprague-Dawley strain were randomly distributed into two experimental groups: Control group (vehicle: corn oil, by gavage) and ED Mix group: received 32.11 mg/kg/day of the ED mixture diluted in corn oil (2 ml/kg), by gavage, from gestational day 7 (DG7) to post-natal day 21 (DPN21). After weaning at DPN22, the male pups continued to receive the complete DE mixture until they were 220 days old when they were euthanized. The ED Mix decreased the epithelial compartment, increased the fractal dimension, and decreased glandular dilation. In addition, low-grade prostatic intraepithelial neoplasia was observed in addition to regions of epithelial atrophy in the group exposed to the ED Mix. Exposure to the mixture decreased both types I and III collagen area in the stroma. We concluded that the ED Mix was able to cause alterations in the prostatic histoarchitecture and induce the appearance of preneoplastic lesions.

High-Intensity Interval Training Minimizes the Deleterious Effects of Arterial Hypertension on the Urinary Bladder of Spontaneously Hypertensive Rats.

Arterial hypertension promotes urological complications by modifying the functional capacity of the urinary bladder. On the other hand, physical exercise has been suggested as a nonpharmacological tool to improve blood pressure regulation. High-intensity interval training (HIIT) can effectively increase peak oxygen consumption, body composition, physical fitness, and health-related characteristics of adults; however, its action on the urinary bladder is little discussed. In the present study, we verified the effect of HIIT on the modulation of the redox state, morphology, and inflammatory and apoptotic processes of the urinary bladder of hypertensive rats. Spontaneously hypertensive rats (SHR) were divided into two groups: SHR sedentary and SHR submitted to HIIT. Arterial hypertension promoted an increase in the plasma redox state, modified the volume of the urinary bladder, and increased collagen deposition in detrusor muscle. It was also possible to identify, in the sedentary SHR group, an increase in inflammatory markers such as IL-6 and TNF-α in the urinary bladder, as well as a reduction in BAX expression. However, in the HIIT group, reduced blood pressure levels were observed, together with an improvement in morphology, such as a decrease in collagen deposition. HIIT also regulated the proinflammatory response, promoting increases in IL-10 and BAX expressions and in the number of plasma antioxidant enzymes. The present work highlights the intracellular pathways involved with the oxidative and inflammatory capacity of the urinary bladder and the potential effect of HIIT on the regulation of the urothelium and detrusor muscle of hypertensive rats.

Physical exercise regulates apoptosis and prostatic inflammatory effects induced by high-fat diet in PPAR-alpha deleted mice.

The high-fat diet (HFD) promotes obesity and develops inflammation, causing dysregulation of energy metabolism and prostatic neoplastic tissue changes. PPARɑ deletion leads to loss of homeostasis between the pro and anti-inflammatory response, and dysregulation of lipid metabolism, causing changes in different physiological processes and damage to the prostate. On the other hand, aerobic physical exercise has been suggested as a non-pharmacological tool to improve energy metabolism and cellular metabolism in the prostate, however, the underlying molecular mechanism remains unclear. the current study aimed to evaluate PPARα as a possible regulator of the protective effects of aerobic physical exercise in the prostate by examining prostatic alterations in wild-type and PPARα deletion mice fed a standard diet or an HFD. Wild-type and PPARα-null mice were fed a standard or HFD diet for 12 weeks, and submitted to aerobic physical exercise for 8 weeks. The HFD promoted the increase of inflammatory markers IL-6, TNF-α, NF-kB, and an increase of inflammatory foci in animals in both genotypes. Although the PPARα deletion animals submitted to the aerobic physical exercise were not able to regulate response pro-inflammatory, but promoted an increase in IL-10 in the prostate. In animals WT, the aerobic physical exercise, reduced all inflammatory markers, improve the inflammatory response, and showed a higher expression of BAX and IL-10 proteins was protective against prostatic tissue lesions. Suggested that PPARα deletion associated with HFD suppressed apoptosis and increased damage prostate. On other hand, aerobic physical exercise improves prostatic tissue by increasing the response to anti-inflammatory and apoptosis protein.

Physical exercise and the functions of microRNAs.

MicroRNAs (miRNAs) control RNA translation and are a class of small, tissue-specific, non-protein-coding RNAs that maintain cellular homeostasis through negative gene regulation. Maintenance of the physiological environment depends on the proper control of miRNA expression, as these molecules influence almost all genetic pathways, from the cell cycle checkpoint to cell proliferation and apoptosis, with a wide range of target genes. Dysregulation of the expression of miRNAs is correlated with several types of diseases, acting as regulators of cardiovascular functions, myogenesis, adipogenesis, osteogenesis, hepatic lipogenesis, and important brain functions. miRNAs can be modulated by environmental factors or external stimuli, such as physical exercise, and can eventually induce specific and adjusted changes in the transcriptional response. Physical exercise is used as a preventive and non-pharmacological treatment for many diseases. It is well established that physical exercise promotes various benefits in the human body such as muscle hypertrophy, mental health improvement, cellular apoptosis, weight loss, and inhibition of cell proliferation. This review highlights the current knowledge on the main miRNAs altered by exercise in the skeletal muscle, cardiac muscle, bone, adipose tissue, liver, brain, and body fluids. In addition, knowing the modifications induced by miRNAs and relating them to the results of prescribed physical exercise with different protocols and intensities can serve as markers of physical adaptation to training and responses to the effects of physical exercise for some types of chronic diseases. This narrative review consists of randomized exercise training experiments with humans and/or animals, combined with analyses of miRNA modulation.