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Methylene-tetrahydrofolate reductase (MTHFR) and paraoxonase 1 (PON1) gene polymorphisms have been associated with hyperhomocysteinemia and oxidative stress increase, that are established cardiovascular risk factors. Given that intense physical activity may increase the susceptibility to adverse cardiovascular outcomes, here we investigated the effects of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms on cardiovascular risk markers in twenty-eight male water polo elite players. The mean plasma levels of homocysteine (Hcy) and advanced oxidation protein products (AOPP) were above reference limits in resting conditions, and increased after competition. Moreover, a positive correlation was found between Hcy and AOPP concentrations, and also between their variations (ratio post-exercise/pre-exercise values) and the variations of lactic dehydrogenase (LDH) and creatine kinase (CK) activities, known as muscle damage markers. The highest Hcy and AOPP values were found in subjects having either MTHFR CT/AC or TT/AA, and PON1 QR192 genotype, respectively. After exercise, Hcy concentrations significantly increased in CT/AC or TT/AA subjects than in athletes having other MTHFR genotypes. A training-induced increase in plasma levels of LDH and CK activities, as well as myoglobin concentrations, was also observed, even if significant differences were found only for CK activity in athletes with MTHFR CT/AC or TT/AA athletes.

Acute exercise is known to induce oxidative stress. Here we assessed the effects of gene polymorphisms SOD2 A16V, CAT −844 G>A, and GPx-1 rs1800668 C>T on oxidative stress markers in 28 elite water polo male players prior to and after a routinely programmed friendly match. The mean plasma concentrations of derivatives of reactive oxygen metabolites (dROMs), as well as lactic dehydrogenase (LDH) activity, creatine kinase (CK) activity, CK-MB, and myoglobin, were significantly increased after exercise, while blood antioxidant potential (BAP) and total free thiols were significantly decreased, compared with those measured before exercise. Advanced oxidation protein products (AOPP) were also increased after exercise but not significantly. We observed that water polo players having either AV16 or VV16 SOD genotype exhibited a significant increase of postexercise AOPP, LDH, CK, and myoglobin plasma levels in comparison with wild-type athletes. Water polo players having either CAT −844 GA or GPx1 CT genotype showed a significant increase of postexercise dROMs plasma levels and, respectively, GPx and CAT enzyme activities in comparison with wild-type subjects. These preliminary results suggest that the screening for gene variants of antioxidant enzymes could be useful to assess individual susceptibility to oxidative stress and muscle damage in water polo players.

Objectives To investigate the distribution of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms, known to be involved in hyperhomocysteinemia-related cardiovascular risk, in elite athletes. Design and methods Genetic background at MTHFR and PON1 loci and plasma levels of homocysteine, folate, vitamin B 12 and advanced oxidation protein product (AOPP) levels were assessed in thirty-seven 400 m male hurdlers and thirty-four sedentary subjects. Results Homocysteine plasma levels and AOPPs were significantly higher in hurdlers bearing the TT677/AA1298 diplotype than in both hurdlers and sedentary subjects with other diplotypes. A positive dependence between either homocysteine or AOPP plasma levels and MTHFR , but not PON1 genotype, was observed in hurdlers. Conclusions Elite hurdlers, having an unfavorable MTHFR genotype are exposed to increased cardiovascular risk, dependent on alterations of homocysteine and AOPP plasma levels.

Recent evidence emphasized that transglutaminase 2 (TG2), a protein cross-linking enzyme, may play a role in the early phase of inflammation. High levels of TG2 have been associated with the constitutive activation of nuclear factor-kappa B (NF-κB) that is considered the main regulator of inflammation. In this context, the receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-κB have extensive functions in the regulation of cytokine secretion associated with different pathological conditions. The human periodontal ligament (HPDL) cells, which express and secrete osteoprotegerin (OPG) and RANKL, represent an useful "ex vivo" model for monitoring cell response in inflammatory microenvironments, such as periodontitis-dependent tissue response. Thus, we evaluated TG2 expression and alterations in RANKL/OPG ratio occurring in cultured HPDL cells. The HPDL cells were obtained from patients with chronic periodontitis (CP) and healthy subjects. We observed the up-regulation of some inflammatory markers, such as IL-6, TNF-α, and HMGB-1, and at the same time an increase in TG2 mRNA levels in HPDL cells from CP patients compared with healthy subjects. We found a positive correlation between RANKL/OPG ratio and TG2 mRNA levels in HPDL cells from CP patients. In the parallel experiments, we demonstrated that TG2 inhibition reduced RANKL expression in both HPDL cells from CP patients and monocytes differentiated to macrophages by tetradecanoyl phorbol acetate treatment. Given the RANKL key role in NF-κB pathway and the observed up-regulation of pro-inflammatory cytokines, our data suggest that TG2 may be involved in molecular mechanisms of inflammatory response occurring in periodontal disease.

Several experimental approaches have demonstrated that transglutaminase 2 (TG2) increased activity is involved in monocyte activation and inflammatory response. Preliminary results also demonstrate a TG-mediated post-translational modification of phospholipase A2 (PLA2), which catalyzes the release of arachidonic acid from its lipid storage sites. The control of PLA2-mediated production of eicosanoids has been found to be of great benefit for inflammatory disease treatment. However, the identification of the mechanisms of PLA2 activation is a very complex issue, because of the presence of multiple PLA2 forms. The aim of this study was to characterize the interactions between TG2 and sPLA2 in LPS-stimulated THP-1 cells, which were treated with TPA to induce early differentiated macrophage-type model. We demonstrated that increases in TG2 enzyme activity and protein expression may be considered an early event in monocyte/macrophage activation by LPS. Under these conditions, TG2 protein was co-immunoprecipitated with PLA2 by monoclonal antibody directed against the secretory form of the enzyme (sPLA2-V). Concomitantly, the PLA2 enzyme activity increased in TPA-treated cells exposed to LPS; these high levels of enzyme activity were significant reduced by R283, a site-specific inhibitor of TG2. Moreover, confocal laser scanning microscopy analysis of double-immunostained cytochemical specimens confirmed a co-localization of BAPA-labeled proteins and sPLA2-V in LPS-treated cells. These findings give evidence of a complex TG2/sPLA2-V, suggesting the possibility that sPLA2-V is a substrate for TG2. These results demonstrated that TG2 increases produced a sustained activation of PLA2 activity, suggesting a functional interaction between these enzymes in the regulation of inflammatory response.