This study aimed to assess the changes in red blood cell (RBC) energy status and plasma purine metabolites concentration over a one-year training cycle in endurance-trained (EN; n = 11, 20-26 years), and sprint-trained (SP; n = 11, 20-30 years) competitive athletes in comparison to recreationally-trained individuals (RE; n = 11, 20-26 years). Somatic, physiological, and biochemical variables were measured in four training phases differing in exercise load profile: transition, general, specific, and competition. Significantly highest values of RBC adenylate energy charge (AEC; p ≤ 0.001), ATP-to-ADP and ADP-to-AMP ratios (p ≤ 0.05), and plasma levels of adenosine (Ado; p ≤ 0.05) were noted in the competition phase in the EN and SP, but not in the RE group. Significantly lowest plasma levels of adenosine diphosphate (ADP; p ≤ 0.05), adenosine monophosphate (AMP; p ≤ 0.001), inosine (Ino; p ≤ 0.001), and hypoxanthine (Hx; p ≤ 0.001) accompanied by higher erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity (p ≤ 0.001), were observed in the competition phase in both athletic groups. No significant alterations were found in the erythrocyte concentration of guanine nucleotides in any group. In conclusion, periodized training of competitive athletes' results in a favorable adaptation of RBC metabolism. The observed changes cover improved RBC energy status (increased AEC and ATP/ADP ratio) and reduced purine loss with more efficient erythrocyte purine pool recovery (increased HGPRT activity and plasma levels of Ado; decreased Hx and Ino concentration).Metabolites 2020, 10, 5 2 of 15 to sedentary humans, besides increased erythropoiesis, there is also observed enhanced erythrocyte turnover and an increase in the number of young red blood cells [2,3].The RBCs' vitality, resilience, and functioning rely on their energy metabolism, mainly glycolysis, which is the only source of adenosine triphosphate (ATP) in RBC [7]. Since ATP resynthesis involves multistep metabolic pathways, the amount of RBC energy resources is usually described by the concentration of ATP, adenosine triphosphate/adenosine diphosphate ratio (ATP/ADP), and the adenylate energy charge (AEC) [8].There are scant studies reporting changes in purine nucleotide catabolite concentration in human and animal erythrocytes in response to single bouts of exercise [3,[9][10][11]. The results obtained from humans suggest that both maximum- [3,9] and moderate-intensity [10] exercise do not significantly affect the total adenylate and guanylate concentration, while adenine (but not guanine) nucleotide concentration in the adenylate pool considerably changes. A substantial post-exercise decrease in adenosine diphosphate (ADP) and adenosine monophosphate (AMP) concentration leads to an increase in ATP/ADP ratio, ADP/AMP ratio, and AEC. These observations are in line with data derived from animals [11].The research conducted so far demonstrated that there were significant differences between trained and sedentary individuals in erythrocyte energetics ...

Cell-based immunotherapies can provide safe and effective treatments for various disorders including autoimmunity, cancer, and excessive proinflammatory events in sepsis or viral infections. However, to achieve this goal there is a need for deeper understanding of mechanisms of the intercellular interactions. Regulatory T cells (Tregs) are a lymphocyte subset that maintain peripheral tolerance, whilst mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitor cells. Despite coming from different origins, Tregs and MSCs share immunoregulatory properties that have been tested in clinical trials. Here we demonstrate how direct and indirect contact with allogenic MSCs improves Tregs’ potential for accumulation of immunosuppressive adenosine and suppression of conventional T cell proliferation, making them more potent therapeutic tools. Our results also demonstrate that direct communication between Tregs and MSCs is based on transfer of active mitochondria and fragments of plasma membrane from MSCs to Tregs, an event that is HLA-dependent and associates with HLA-C and HLA-DRB1 eplet mismatch load between Treg and MSC donors.

Influence of various energetic substrates on ATP content and adenine nucleotide catabolism in African catfish, Clarias gariepinus spermatozoa was investigated. Present data indicate that sperm storage at 4°C in the presence of different energetic substrates leads to time dependent ATP depletion. Among the substrates studied (i.e. glycine, glucose, or lactate plus pyruvate), the lactate plus pyruvate seems to be the most favourable substrate to maintain ATP concentration. ATP depletion is associated with increase of the AMP content, while ADP concentration is changing only slightly. Moreover, significant increase in hypoxanthine content both in the sperm and a storage medium was found. Adenine nucleotide energy charge (AEC) decreased significantly during the first 24 h when sperm was stored in the presence of glycine. During the same period, only slight decrease in AEC was observed in spermatozoa stored in the presence of glucose and no significant changes were found in the presence of lactate plus pyruvate. A further decrease in AEC was observed until 120 h of storage in the medium containing glycine, lactate plus pyruvate or glucose. However, the changes were relatively small when spermatozoa were stored in the presence of lactate plus pyruvate. Important finding is that in contrast to the results reported recently, AEC value in fresh milt (at 0 time of storage) was in the normal range. The present study shows that African catfish spermatozoa are able to maintain physiological level of ATP and AEC when they are stored in the presence of favourable energetic substrates. In conclusion, the results of this investigation suggest that successful short-term storage of African catfish milt depends on energetic substrates supply.Abbreviations: AEC -adenine nucleotide energy charge; ADP -adenosine diphosphate; AMP -adenosine monophosphate; ATP -adenosine triphosphate; cAMP -cyclic AMP; HPLC -high performance liquid chromatography; IMP -inosine monophosphate; TAN -total adenine nucleotide.

No abstract

Significant improvement of hemodynamics following propionyl-L-carnitine administration in diabetic patients undergoing on-bypass coronary surgery was accompanied by reduced trans-cardiac endothelin difference and rapid hypoxanthine washout during reperfusion suggesting improvement of metabolism or vascular function.

Changes in purine derivatives may be considered as signs of training-induced metabolic adaptations. The purpose of this study was to assess the effect of a 1-year training cycle on the response of hypoxanthine (Hx) concentration and Hx-guanine phosphoribosyltransferase (HGPRT) activity. Three groups of middle-aged male runners were examined: 11 elite master runners (EL; 46.0 ± 3.8 years), 9 amateur runners (AM; 45.1 ± 4.7 years), and 10 recreational runners (RE; 45.9 ± 6.1 years). Plasma Hx concentration and erythrocyte HGPRT activity were measured in three characteristic training phases of the annual cycle. Significant differences in post-exercise Hx concentration and resting HGPRT activity were demonstrated between the EL, AM, and RE groups across consecutive training phases. The EL group showed lowest Hx concentration and highest HGPRT activity compared to the AM and RE groups. Analogous differences were observed between the AM and RE groups during specific preparation. For the EL group, the changes were observed across all examinations and the lowest Hx concentration and highest HGPRT activity were found in the competition phase. Significant change was also revealed in the AM group between the general and specific preparation, but not in the competition phase. No significant changes were found in the RE runners who did not use anaerobic exercise in their training. In conclusion, a long-lasting endurance training, incorporating high-intensity exercise, results in significant changes in purine metabolism, whereas training characterized by constant low-intensity exercise does not. Plasma Hx concentration and erythrocyte HGPRT activity may be sensitive indicators of training adaptation and training status in middle-aged athletes.

No abstract

Nucleotide metabolism and signalling is directly linked to myocardial function. Therefore analysis how diversity of genes coding nucleotide metabolism related proteins affects clinical progress of heart disease could provide valuable information for development of new treatments. Several studies identified that polymorphism of AMP deaminase 1 gene (AMPD1), in particular the common C34T variant of this gene was found to benefit patients with heart failure and ischemic heart disease. However, these findings were inconsistent in subsequent studies. This prompted our detailed analysis of heart transplant recipients that revealed diverse effect: improved early postoperative cardiac function associated with C34T mutation in donors, but worse 1-year survival. Our other studies on the metabolic impact of AMPD1 C34T mutation revealed decrease in AMPD activity, increased production of adenosine and de-inhibition of AMP regulated protein kinase. Thus, genetic, clinical and biochemical studies revealed that while long term attenuation of AMPD activity could be deleterious, transient inhibition of AMPD activity before acute cardiac injury is protective. We suggest therefore that pharmacological inhibition of AMP deaminase before transient ischemic event such as during ischemic heart disease or cardiac surgery could provide therapeutic benefit.