The basic chemistry of exercise-induced DNA oxidation:oxidative damage, redox signalling and their interplay

Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1) redox signalling and (2) macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (·OH) and hydrogen peroxide (H2O2) as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ·OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation

Influence of vitamin C and vitamin E on redox signalling:implications for exercise adaptations

The exogenous antioxidants vitamin C (ascorbate) and vitamin E (α-tocopherol) often blunt favourable cell signalling responses to exercise, suggesting that redox signalling contributes to exercise adaptations. Current theories posit that this antioxidant paradigm interferes with redox signalling by attenuating exercise-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. The well-documented in vitro antioxidant actions of ascorbate and α-tocopherol and characterisation of the type and source of the ROS/RNS produced during exercise theoretically enables identification of the redox-dependent mechanism responsible for the blunting of favourable cell signalling responses to exercise. This review aimed to apply this reasoning to determine how the aforementioned antioxidants might attenuate exercise-induced ROS/RNS production. The principal outcomes of this analysis are (1) neither antioxidant is likely to attenuate nitric oxide signalling either directly (reaction with nitric oxide) or indirectly (reaction with derivatives, e.g. peroxynitrite) (2) neither antioxidant reacts appreciably with hydrogen peroxide, a key effector of redox signalling (3) ascorbate but not α-tocopherol has the capacity to attenuate exercise-induced superoxide generation and (4) alternate mechanisms, namely pro-oxidant side reactions and/or reduction of bioactive oxidised macromolecule adducts, are unlikely to interfere with exercise-induced redox signalling. Out of all the possibilities considered, ascorbate mediated suppression of superoxide generation with attendant implications for hydrogen peroxide signalling is arguably the most cogent explanation for blunting of favourable cell signalling responses to exercise. However, this mechanism is dependent on ascorbate accumulating at sites rich in NADPH oxidases, principal contributors to contraction mediated superoxide generation, and outcompeting nitric oxide and superoxide dismutase isoforms. The major conclusions of this review are: (1) direct evidence for interference of ascorbate and α-tocopherol with exercise-induced ROS/RNS production is lacking (2) theoretical analysis reveals that both antioxidants are unlikely to have a major impact on exercise-induced redox signalling and (3) it is worth considering alternate redox-independent mechanisms

Hybridization capture reveals evolution and conservation across the entire koala retrovirus genome

The koala retrovirus (KoRV) is the only retrovirus known to be in the midst of invading the germ line of its host species. Hybridization capture and next generation sequencing were used on modern and museum DNA samples of koala (Phascolarctos cinereus) to examine ca. 130 years of evolution across the full KoRV genome. Overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. A total of 138 polymorphisms were detected, of which 72 were found in more than one individual. At every polymorphic site in the museum koalas, one of the character states matched that of modern KoRV. Among non-synonymous polymorphisms, radical substitutions involving large physiochemical differences between amino acids were elevated in env, potentially reflecting anti-viral immune pressure or avoidance of receptor interference. Polymorphisms were not detected within two functional regions believed to affect infectivity. Host sequences flanking proviral integration sites were also captured; with few proviral loci shared among koalas. Recently described variants of KoRV, designated KoRV-B and KoRV-J, were not detected in museum samples, suggesting that these variants may be of recent origin.Kyriakos Tsangaras, Matthew C. Siracusa, Nikolas Nikolaidis, Yasuko Ishida, Pin Cui, Hanna Vielgrader, Kristofer M. Helgen, Alfred L. Roca, Alex D. Greenwoo

Effects of moderate- vs. high-intensity interval training on physical fitness, enjoyment, and affective valence in overweight/obese female adolescents: a pre-/post-test study

OBJECTIVE The aim of this study was to compare the effects of 12-week moderate-intensity interval training (MIIT) vs. high-intensity interval training (HIIT) on body composition, physical fitness, and psychological valence in overweight/obese (OW/OB) female adolescents. PATIENTS AND METHODS Thirty-eight OW/OB female students were randomized into HIIT (n=13), MIIT (n=13) or control (n=12) groups. The participants underwent a 12-week interval-training program at 100% to 110% and 60% to 75% of maximal aerobic speed for HIIT and MIIT, respectively. The control group kept their usual physical activity without completing the training program. Pre- and post-training measurements were performed to assess body composition, aerobic capacity, and anaerobic performance (using selected tests evaluating speed, jumping ability, and strength). Ratings of perceived exertion and the feeling scale were evaluated every three weeks. Enjoyment was measured at the end of the program. A two-way analysis of variance with repeated measurements was applied to test for "group×time" interactions for body composition, physical fitness, and affective variables. RESULTS Significant "group×time" interactions were detected for aerobic and anaerobic performance, body composition indices, and the feeling scale. HIIT resulted in more noticeable improvements in body composition and physical performance than MIIT, while no significant changes were found in the control group. Throughout the program, the feeling score has progressively increased in the MIIT group but decreased in the HIIT group. Ratings of the perceived exertion have increased in both groups, more noticeably in the HIIT group. At the end of the program, the MIIT group showed a higher enjoyment score. CONCLUSIONS Despite offering better body composition improvement and physical fitness enhancement, HIIT offered lesser enjoyment and affective valence than MIIT in OW/OB female adolescents. MIIT might be an alternative time-efficient protocol for improving health in this population