C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension.

Deficiency of S6 kinase (S6K) extends the lifespan of multiple species, but the underlying mechanisms are unclear. To discover potential effectors of S6K-mediated longevity, we performed a proteomics analysis of long-lived rsks-1/S6K C. elegans mutants compared to wild-type animals. We identified the arginine kinase ARGK-1 as the most significantly enriched protein in rsks-1/S6K mutants. ARGK-1 is an ortholog of mammalian creatine kinase, which maintains cellular ATP levels. We found that argk-1 is possibly a selective effector of rsks-1/S6K-mediated longevity and that overexpression of ARGK-1 extends C. elegans lifespan, in part by activating the energy sensor AAK-2/AMPK. argk-1 is also required for the reduced body size and increased stress resistance observed in rsks-1/S6K mutants. Finally, creatine kinase levels are increased in the brains of S6K1 knockout mice. Our study identifies ARGK-1 as a longevity effector in C. elegans with reduced RSKS-1/S6K levels.

Synergistic role of ADP and Ca(2+) in diastolic myocardial stiffness.

Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall. Increased actomyosin interactions may significantly limit diastolic capacity, however, direct evidence is absent. From experiments at the cellular and whole organ level, in humans and rats, we show that actomyosin-related force development contributes significantly to high diastolic stiffness in environments where high ADP and increased diastolic [Ca(2+) ] are present, such as the failing myocardium. Our basal study provides a mechanical mechanism which may partly underlie diastolic dysfunction. Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross-bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross-bridge interactions are dependent on cytosolic [Ca(2+) ] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca(2+) handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca(2+) ] promotes diastolic cross-bridge formation and force generation and thereby increases diastolic stiffness. ADP dose-dependently increased force production in the absence of Ca(2+) in membrane-permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca(2+) both in human and rat membrane-permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca(2+) ] revealed a 76 ± 1% contribution of cross-bridge interaction to total diastolic stress in rat membrane-permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme-isolated intact rat cardiomyocytes impaired diastolic re-lengthening associated with diastolic Ca(2+) overload. In isolated Langendorff-perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca(2+) ]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross-bridges, even at low Ca(2+) , and thereby increase myocardial stiffness.

Treatment of dyslipidemia with statins and physical exercises: recent findings of skeletal muscle responses.

Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords "statin" AND "exercise" AND "muscle", restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible.

Treatment of Dyslipidemia with Statins and Physical Exercises: Recent Findings of Skeletal Muscle Responses / Tratamento das Dislipidemias com Estatinas e Exercícios Físicos: Evidências Recentes das Respostas Musculares

Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords “statin” AND “exercise” AND “muscle”, restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible.

A associação do tratamento medicamentoso por estatinas com a prática de exercícios físicos pode reduzir substancialmente o risco de mortalidade cardiovascular de indivíduos dislipidêmicos, porém sua realização vem sendo associada à exacerbação de quadros miopáticos. O presente trabalho teve como objetivo apresentar os resultados mais recentes da literatura específica sobre os efeitos da associação de estatinas ao exercício físico na musculatura esquelética. Para tanto, realizou-se levantamento da literatura nas bases de dados PubMed e SciELO, utilizando a combinação dos unitermos: “estatina/estatinas” AND “exercício” AND “músculo” (“statin” AND “exercise” AND “muscle”), sendo selecionados apenas artigos originais publicados entre janeiro de 1990 e novembro de 2013. Foram analisados 16 artigos que avaliaram o efeito da associação das estatinas com exercício agudo ou crônico na musculatura esquelética. Os resultados dos estudos apontaram que atletas podem experimentar efeitos deletérios na musculatura esquelética quando do uso de estatinas, visto que os quadros de exacerbação da lesão muscular pelo exercício foram mais frequentes com treinamento intenso ou exercícios agudos excêntricos e extenuantes. O treinamento físico moderado, por sua vez, quando associado às estatinas, não aumenta os relatos de dor nem os níveis de creatina quinase, além de acarretar ganhos nas funções musculares e metabólicas advindas do treinamento. Sugere-se, portanto, que pacientes dislipidêmicos em tratamento com estatinas sejam expostos ao treinamento físico aeróbio combinado a exercícios resistidos, de intensidade moderada, em três sessões semanais, sendo que a oferta do treinamento físico previamente à administração do tratamento medicamentoso, quando possível, faz-se desejável.

CKMT1 regulates the mitochondrial permeability transition pore in a process that provides evidence for alternative forms of the complex.

The permeability transition pore (PT-pore) mediates cell death through the dissipation of the mitochondrial membrane potential (ΔΨm). Because the exact composition of the PT-pore is controversial, it is crucial to investigate the actual molecular constituents and regulators of this complex. We found that mitochondrial creatine kinase-1 (CKMT1) is a universal and functionally necessary gatekeeper of the PT-pore, as its depletion induces mitochondrial depolarization and apoptotic cell death. This can be inhibited efficiently by bongkrekic acid, a compound that is widely used to inhibit the PT-pore. However, when the 'classical' PT-pore subunits cyclophilin D and VDAC1 are pharmacologically inhibited or their expression levels reduced, mitochondrial depolarization by CKMT1 depletion remains unaffected. At later stages of drug-induced apoptosis, CKMT1 levels are reduced, suggesting that CKMT1 downregulation acts to reinforce the commitment of cells to apoptosis. A novel high-molecular-mass CKMT1 complex that is distinct from the known CKMT1 octamer disintegrates upon treatment with cytotoxic drugs, concomitant with mitochondrial depolarization. Our study provides evidence that CKMT1 is a key regulator of the PT-pore through a complex that is distinct from the classical PT-pore.

Markers of muscle damage and performance recovery after exercise in the heat.

PURPOSE: This study aimed to determine whether competitive intermittent exercise in the heat affects recovery, aggravates markers of muscle fiber damage, and delays the recovery of performance and muscle glycogen stores. METHODS: Plasma creatine kinase, serum myoglobin, muscle glycogen, and performance parameters (sprint, endurance, and neuromuscular testing) were evaluated in 17 semiprofessional soccer players before, immediately after, and during 48 h of recovery from a match played in 43°C (HOT) and compared with a control match (21°C with similar turf and setup). RESULTS: Muscle temperature was ∼1°C higher (P < 0.001) after the game in HOT compared with control and reached individual values between 39.9°C and 41.1°C. Serum myoglobin levels increased by more than threefold after the matches (P < 0.01), but values were not different in HOT compared with control, and they were similar to baseline values after 24 h of recovery. Creatine kinase was significantly elevated both immediately and 24 h after the matches, but the response after HOT was reduced compared with control. Muscle glycogen responses were similar across trials and remained depressed for more than 48 h after both matches. Sprint performance and voluntary muscle activation were impaired to a similar extent after the matches (sprint by ∼2% and voluntary activation by ∼1.5%; P < 0.05). Both of these performance parameters as well as intermittent endurance capacity (estimated by a Yo-Yo IR1 test) were fully recovered 48 h after both matches. CONCLUSION: Environmental heat stress does not aggravate the recovery response from competitive intermittent exercise associated with elevated muscle temperatures and markers of muscle damage, delayed resynthesis of muscle glycogen, and impaired postmatch performance.

Recovery after an intermittent test.

The purpose of this study was to analyse the impact of an intermittent test reproducing the soccer running activity profile on physical performance, subjective ratings and biochemical parameters throughout 72 h recovery. 8 professional soccer players performed the intermittent test on a non-motorised treadmill and data was collected before, immediately after, 24, 48 and 72 h after the test. Squat jump (SJ), countermovement jump (CMJ), peak isometric force (IFpeak), 6-s sprint, repeated sprints test (RS), perceptual ratings (fatigue, muscle soreness, stress), creatine kinase ([CK]) and uric acid ([UA]) were analyzed. After the test, a mean reduction in countermovement jump performance of -8.2% (CI: -12.9 to -3.4, p<0.01) was observed, while perceived fatigue (+2.1±1.7 a.u.; p<0.05), perceived muscle soreness (+1.8±1.5 a.u.; p<0.05), perceived stress (+1.6±1.5 a.u.; p<0.05), creatine kinase (+171±77 IU x l(-1); p<0.01) and uric acid (+168±89 Umol x l(-1); p<0.01) concentrations were significantly increased relative to baseline. No significant effect was found for SJ, IFpeak, 6-s sprint, RS immediately after and throughout the 72 h following the test. In conclusion, soccer running performance does not appear to be the main cause of post soccer match-induced fatigue. Physical data provided by video match analysis systems is insufficient to accurately estimate the level of match fatigue.

Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression.

INTRODUCTION: Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (k(for)) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases k(for) in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls. METHODS: Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla (31)Phosphorus magnetic resonance spectroscopy ((31)PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate k(for). The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline k(for) and changes in k(for) were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with k(for) changes using repeated measures linear regression. RESULTS: The k(for) of CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The k(for) for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis, depression severity decreased with CoQ10 treatment in the group with BPD (F (3,7) = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t (9) = -2.40, P = .04) and 4 (t (9) = -3.80, P = .004). CONCLUSIONS: This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the k(for) of CK but did observe a trend that would require confirmation in a larger study. An exploratory analysis suggested a reduction in depression symptom severity during treatment with high-dose CoEnzyme Q10 for older adults with BPD. Further studies exploring alterations of high-energy phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a randomized controlled trial are both warranted.

A comparison of muscle damage, soreness and performance following a simulated contact and non-contact team sport activity circuit.

The aim was to compare the effect of a simulated team sport activity circuit (reflective of the activity demands of Australian football) either with or without body 'contact' on muscle soreness, damage, and performance when the circuit was repeated 48 h later. Eleven male, team-sport athletes completed a 'non-contact' (NCON) and a 'contact' (CON) version of the team sport activity circuit in a crossover design with at least 1 week between trials. The effect of CON and NCON on repeated 15m sprint and vertical jump performance was assessed by completing the same version of the circuit 48 h after the initial trial. The effect on perceived soreness and blood markers of muscle damage and inflammation was also determined. Subsequent performance was affected to a greater extent by CON, with both best and mean sprint times significantly slower 48h following CON (p<0.05), while performance was maintained after NCON. Best and mean vertical jump performance was significantly impaired following CON (p<0.05), while only best vertical jump was affected by NCON (p<0.05). Perceived soreness and pressure sensitivity were elevated following both NCON and CON (p<0.001); however, the increase in soreness was greater with CON (p=0.012). Both CON and NCON resulted in elevated serum creatine kinase, myoglobin and lactate dehydrogenase, while c-reactive protein increased following CON but not NCON. In conclusion, Greater perceived soreness and decrements in performance of the simulated team sport activity circuit when repeated 48 h later were observed following CON.

Creatine kinase and endocrine responses of elite players pre, during, and post rugby league match play.

The purpose of the present study was to (a) examine player-movement patterns to determine total distance covered during competitive Rugby League match play using global positioning systems (GPSs) and (b) examine pre, during, and postmatch creatine kinase (CK) and endocrine responses to competitive Rugby League match play. Seventeen elite rugby league players were monitored for a single game. Player movement patterns were recorded using portable GPS units (SPI-Pro, GPSports, Canberra, Australia). Saliva and blood samples were collected 24 hours prematch, 30 minutes prematch, 30 minutes postmatch, and then at 24-hour intervals for a period of 5 days postmatch to determine plasma CK and salivary testosterone, cortisol, and testosterone:cortisol ratio (T:C). The change in the dependent variables at each sample collection time was compared to 24-hour prematch measures. Backs and forwards traveled distances 5,747 ± 1,095 and 4,774 ± 1,186 m, respectively, throughout the match. Cortisol and CK increased significantly (p < 0.05) from 30 minutes prematch to 30 minutes postmatch. Creatine kinase increased significantly (p < 0.05) postmatch, with peak CK concentration measured 24 hours postmatch (889.25 ± 238.27 U·L). Cortisol displayed a clear pattern of response with significant (p < 0.05) elevations up to 24 hours postmatch, compared with 24 hours prematch. The GPS was able to successfully provide data on player-movement patterns during competitive rugby league match play. The CK and endocrine profile identified acute muscle damage and a catabolic state associated with Rugby League match play. A return to normal T:C within 48 hours postmatch indicates that a minimum period of 48 hours is required for endocrine homeostasis postcompetition. Creatine kinase remained elevated despite 120 hours of recovery postmatch identifying that a prolonged period of at least 5 days modified activity is required to achieve full recovery after muscle damage during competitive Rugby League match play.

The effect of oral vs. Intravenous rehydration on circulating myoglobin and creatine kinase.

Physical activity of significant intensity and duration may cause varying degrees of skeletal muscle damage, but it is unclear whether mode of rehydration will attenuate muscle tissue disruption caused by exercise in the heat. To examine the effects of the mode of rehydration on markers of muscle damage (myoglobin and creatine kinase [CK]), 11 healthy active men (age = 23 +/- 4 years, body mass = 80.9 +/- 3.9 kg, height = 180.5 +/- 5.4 cm) completed 4 experimental trials consisting of an exercise dehydration protocol (to -4% of baseline body mass), followed by a rehydration period (oral, intravenous [IV], oral and IV combined, and ad libitum), and finishing with an intense exercise challenge that included treadmill running and sprinting and a box lifting protocol. During rehydration, subjects returned to -2% of baseline body mass unless completing the ad libitum trial during which they consumed fluids as thirst dictated. Myoglobin (Mb) and CK were measured during euhydrated rest. Post-exercise blood was drawn at 1 and 24 hours post exercise challenge for Mb and CK, respectively. Urine was collected during euhydrated rest and 1-hour post exercise challenge for measurement of Mb clearance. Mb concentrations increased significantly from pre (1.06 +/- 0.20, 0.88 +/- 0.07, 1.15 +/- 0.25 and 0.92 +/- 0.06 nmol.L) to post (1.52 +/- 0.28, 1.44 +/- 0.11, 1.71 +/- 0.45 and 1.58 +/- 0.39) for IV, oral, oral and IV combined, and ad libitum, respectively, but were not significantly different among trials. Serum CK concentrations remained within the normal physiological range for all trials. Thus, despite previous research that clearly indicates the benefit of ingesting fluids during exercise to attenuate muscle damage, there were no significant differences between the modes of rehydration on circulating Mb and CK.

Changes in lipid peroxidation and antioxidant capacity during walking and running of the same and different intensities.

The aim was to investigate the changes in lipid peroxidation, antioxidant enzyme activities, and muscle damage in the same and different exercise intensities during walking and running. Fourteen healthy males participated in this study. The subjects' individual preferred walk-to-run transition speeds (WRTS) were determined. Each subject covered a 1.5-mile distance for 4 exercise tests; walking (WRTS-W) and running (WRTS-R) tests at WRTS, 2 kmxh-1 slower walking than WRTS (WRTS-2) and 2 kmxh-1 faster running than WRTS (WRTS+2). Blood samples were taken pre, immediately, and 30 minutes post each test. The changes in (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and creatine kinase activities were measured. Oxygen uptake, carbon dioxide output, oxygen uptake per kilogram of body weight, and heart rate during exercises were significantly higher in both the WRTS-W and the WRTS+2 exercises compared with the WRTS-2 and WRTS-R. Oxygen consumption and energy expenditure were higher in walking than in the running exercise at the preferred WRTS and only WRTS-W exercise significantly increased MDA levels. Catalase activities were increased by WRTS-W, WRTS-R, and WRTS+2 exercises. Changes in SOD and CAT activities were not different between walking and running exercises at the preferred WRTS. Total plasma GSH increased in response to WRTS-W exercise, which could be associated with an increase in MDA. Also, total GSH levels 30 minutes postexercise were significantly lower than postexercise in WRTS-2, WRTS-W, and WRTS+2 exercises. Our results indicate that walking and running exercises at the preferred WRTS have different oxidative stress and antioxidant responses.

Regulation of T cell development and activation by creatine kinase B.

Creatine kinase catalyzes the reversible transfer of the N-phosphoryl group from phosphocreatine to ADP to generate ATP and plays a key role in highly energy-demanding processes such as muscle contraction and flagellar motility; however, its role in signal transduction (which frequently involves ATP-consuming phosphorylation) and consequent cell-fate decisions remains largely unknown. Here we report that creatine kinase B was significantly up-regulated during the differentiation of double-positive thymocytes into single-positive thymocytes. Ectopic expression of creatine kinase B led to increased ATP level and enhanced phosphorylation of the TCR signaling proteins. Consequentially, transgenic expression of creatine kinase B promoted the expression of Nur77 and Bim proteins and the cell death of TCR signaled thymocyte. In addition, the activation, proliferation and cytokine secretion of T cells were also enhanced by the expression of creatine kinase B transgene. In contrast, treatment of T cells with specific creatine kinase inhibitor or creatine kinase B shRNA resulted in severely impaired T cell activation. Taken together, our results indicate that creatine kinase B plays an unexpected role in modulating TCR-mediated signaling and critically regulates thymocyte selection and T cell activation.

Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice.

Creatine kinase (CK) is a phosphotransfer kinase that catalyzes the reversible transfer of a phosphate moiety between ADP and creatine and that is highly expressed in skeletal muscle. In fast glycolytic skeletal muscle, deletion of the cytosolic M isoform of CK in mice (M-CK-/-) leads to a massive increase in the oxidative capacity and of mitochondrial volume. This study was aimed at investigating the transcriptional pathways leading to mitochondrial biogenesis in response to CK deficiency. Wild type and M-CK-/- mice of eleven months of age were used for this study. Gastrocnemius muscles of M-CK-/- mice exhibited a dramatic increase in citrate synthase (+120%) and cytochrome oxidase (COX, +250%) activity, and in mitochondrial DNA (+60%), showing a clear activation of mitochondrial biogenesis. Similarly, mRNA expression of the COXI (mitochondria-encoded) and COXIV (nuclear-encoded) subunits were increased by +103 and +94% respectively. This was accompanied by an increase in the expression of the nuclear respiratory factor (NRF2alpha) and the mitochondrial transcription factor (mtTFA). Expression of the co-activator PGC-1alpha, a master gene in mitochondrial biogenesis was not significantly increased while that of PGC-1beta and PRC, two members of the same family, was moderately increased (+45% and +55% respectively). While the expression of the modulatory calcineurin-interacting protein 1 (MCIP1) was dramatically decreased (-68%) suggesting inactivation of the calcineurin pathway, the metabolic sensor AMPK was activated (+86%) in M-CK-/- mice. These results evidence that mitochondrial biogenesis in response to a metabolic challenge exhibits a unique pattern of regulation, involving activation of the AMPK pathway.

Proteomic approach for caudal trauma-induced acute phase proteins reveals that creatine kinase is a key acute phase protein in amphioxus humoral fluid.

Elevated creatine kinase (CK) in the circulation was generally regarded to be a passive release from muscle damage. We utilized proteomic methodologies to characterize amphioxus humoral fluid APPs in response to caudal trauma, and found several spots of CK alterations with up-regulation and pI shift. Its amount and enzyme activity showed a dynamic pattern of APP in humoral fluid accompanied with a reduction in enzyme activity of muscle, whereas there was no significant difference in CK amount of muscle and the other tissues and in CK enzyme activity of the other tissues between different time points of sample collection following caudal trauma. In addition, CK phosphorylation regulation during injury was not achieved by monoclonal antibodies separately against phosphothreonine, phosphotyrosine, and phosphoserine. These results suggested that the CK elevation of humoral fluid might be from muscle, being an active response to caudal trauma rather than a passive release from muscle damage. Therefore, CK ability in response to caudal trauma should be highly concerned.

Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme.

OBJECTIVE: To investigate the association between muscle-specific creatine kinase (CKMM) gene polymorphism and the effects of endurance training on running economy. METHODS: 102 biologically unrelated male volunteers from northern China performed a 5000-m running programme, with an intensity of 95-105% ventilatory threshold. The protocol was undertaken three times per week and lasted for 18 weeks. Running economy indexes were determined by making the participants run on a treadmill before and after the protocol, and the A/G polymorphism in the 3' untranslated region of CKMM was detected by polymerase chain reaction-restricted fragment length polymorphism (NcoI restriction enzyme). RESULTS: Three expected genotypes for CKMM-NcoI (AA, AG and GG) were observed in the participants. After training, all running economy indexes declined markedly. Change in steady-state consumption of oxygen, change in steady-state consumption of oxygen by mean body weight, change in steady-state consumption of oxygen by mean lean body weight and change in ventilatory volume in AG groups were larger than those in AA and GG groups. CONCLUSIONS: The findings indicate that the CKMM gene polymorphism may contribute to individual running economy responses to endurance training.

[New mechanisms of biological effects of electromagnetic fields].

The production of ATP in mitochondria depends on the magnesium nuclear spin and magnetic moment of a Mg2+ ion in creatine kinase and ATPase. This suggests that enzymatic synthesis of ATP is an ion-radical process and thus depends on the external magnetic field (magnetobiology originates from this fact) and microwave fields, which control the spin states of ion-radical pairs and affect the ATP synthesis. The chemical mechanism of ATP synthesis and the origin of biological effects of electromagnetic (microwave) fields are discussed.

[Magnesium magnetic isotope effect: a key towards mechanochemistry of phosphorylating enzymes as molecular machines].

A discovery of the huge magnesium isotope effect in enzymatic ATP synthesis provides a new insight into mechanochemistry of enzymes as the molecular machines. It has been found that the catalytic activity values of ATPase, creatine kinase and phosphoglycerate kinase are 2 to 4-fold higher once their active sites contain magnetic (25Mg) not spinless, non-magnetic (24Mg, 26Mg), magnesium cation isotopes. This clearly proves that the ATP synthesis is a spin-selective process involving Mg2+ as the electron accepting reagent. The formation of ATP takes place in an ion-radical pair resulted by two partners, ATP oxyradical and Mg+. The magnesium bivalent cation is a key player in this process, this ion transforms the protein molecule mechanics into a mere chemistry. This ion is a most critical detail of structure of the magnesium dependent phosphorylation enzymes as the mechanochemical molecular machines.