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Long non-coding RNAs (lncRNAs) play critical roles in various biological functions and disease processes including cancer. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was initially identified as a lncRNA with elevated expression in primary human non-small cell lung tumors with high propensity to metastasize, and subsequently shown to be highly expressed in numerous other human cancers including breast, ovarian, prostate, cervical, endometrial, gastric, pancreatic, sarcoma, colorectal, bladder, brain, multiple myeloma, and lymphoma. MALAT1 is deeply involved in several physiological processes, including alternative splicing, epigenetic modification of gene expression, cellular senescence, healthy aging, and redox homeostasis. The aim of this work was to investigate the modulation exerted by a single bout of endurance exercise on the level of MALAT1 expression in peripheral blood mononuclear cells (PBMCs) from healthy male donors displaying different training status and redox homeostasis features. Our findings show that MALAT1 is downregulated after acute endurance exercise in subjects whose fitness level guarantee a high expression of SOD1 and SOD2 antioxidant genes and low levels of endogenous oxidative damage. In vitro protocols in Jurkat lymphoblastoid cells exposed to pro-oxidant environment confirmed the link between MALAT1 expression and antioxidant gene modulation, documenting p53 phosphorylation and its recruitment to MALAT1 promoter. Remarkably, analyses of Microarray-Based Gene Expression Profiling revealed high MALAT1 expression in leukemia patients in comparison to healthy control and a significant negative correlation between MALAT1 and SOD1 expression. Collectively our results highlight the beneficial effect of a physically active lifestyle in counteracting aberrant cancer-related gene expression programs by improving the redox buffering capacity.

The phosphodiesterases type 5 (PDE5) inhibitors (PDE5i) (e.g., sildenafil, tadalafil) widely used to treat erectile dysfunction, and for recreational purpose such as sports supplements, may enhance the cGMP-dependent metabolic effects of NO. An increase in NO production, following tadalafil administration, could generate peroxynitrite, the most reactive free radical species causing oxidative injury. We investigate whether the acute supplementation with PDE5i could affect plasma antioxidant status in healthy, physically active humans. A crossover study has been carried out with male volunteers (n=6) supplemented with a single dose of 20 mg tadalafil. Plasma total antioxidant status (TAS) and glutathione (GSH) homeostasis were evaluated immediately before and after 2, 6 and 24 hours of the acute administration.TAS values increased after 2 h (1.01 ± 0.13 Trolox eq. mM) to decrease after 24 h (0.85 ± 0.06) compared to baseline (0.92 ± 0.09). Oxidized glutathione (GSSG) increased from 6 h (3.68 ± 0.55, 4.27 ± 0.97 and 5.09 ± 0.82 GSSG 10-5 M for baseline, 6 h and 24 h respectively). GSH/GSSG ratio decreased (16.85 ± 5.28 and 12.85 ± 2.00 for 6 and 24 h) compared to baseline (18.36 ± 4.92). Our preliminary results show that an acute tadalafil administration affects plasma antioxidant status in healthy physically active men.

Quercetin (Q) functions as antioxidant in vitro, but its effect have been minimally examined in combination with exercise in humans. The purpose of this investigation was to determine the effects of a diet supplemented with 1 g per day of Q for 2 weeks on the erythrocytes oxidative balance before and after an acute bout of eccentric exercise (EE). Fourteen volunteer males were randomly assigned, in a double-blind crossover design, to a placebo or experimental supplemented groups. Blood samples were taken before and after 2 weeks of supplementation under resting and post-exercise conditions. Erythrocytes glutathione (GSH, GSSG, GSH/GSSG), malonaldehyde (TBARs), enzymes antioxidant activities as well as time of hemolysis were evaluated in ex vivo. Quercertin per se did not affect redox homeostasis but increased the time of hemolysis and decreased TBARs levels. Following the EE the Q group displayed a higher GSH/GSSG ratio and a less pronounced increase in TBARs, compared to placebo group. Moreover, we found that GPx enzyme activity were induced after EE only in Q group, while any significant modification of this parameter was detected in placebo group. In conclusion, the Q supplementation may be used as a countermeasure against oxidative stress inducing, in erythrocytes, a cellular adaptation allowing subjects to better cope with the oxidative stress induced by an acute exercise.

Sirtuins are NAD+ dependent deacetylases that play a key role in the regulation of many processes related to homeostasis, such as the regulation of metabolism, apoptosis, DNA repair and inflammatory response. Studies on humans reported a relation between the alteration of their expression and the incidence of various diseases such as metabolic, cardiovascular, cancer and neurodegenerative diseases. According with these findings the maintenance of their optimal level of activity is considered important to ensure a low risk of pathologies related with the aging process. Indeed, SIRT1 has been correlated with the redox homeostasis maintenance and with the levels of oxidative damage, such as those affecting telomeric sequences of DNA. The aim of this study is to verify the correlation between sirtuins’ expression, histone deacetylation and redox status in young and old monozygotic twins. For this study we took advantage from blood samples of young (20-40 years old) and old (70-80 years old) monozygotic twins couple, where we analysed the expression of SIRT1 and SIRT2, Lysine acetylation proteins and Histone H4 acetylation, the protein oxidation through the detection of carbonyl groups have been analysed in PBMCs, plasma level of oxidized and reduced glutathione. The putative increase of SIRT1 and SIRT2 levels that should also lead to an improvement in redox and inflammatory homeostasis, hormonal response to stress, and in the maintenance of telomeric DNA sequences could open an interesting view in this field. Particularly the twin model can help to better understand the interaction between genetic and epigenetic effects in the age-related mechanisms.