Effects of Endurance Training on the Coenzyme Q Redox State in Rat Heart, Liver and Brain at the Tissue and Mitochondrial Levels: Implications for Reactive Oxygen Species Formation and Respiratory Chain Remodeling

Sixteen adult, 4-month-old male Wistar rats were randomly assigned to the training group (n = 8) or the control group (n = 8). We elucidated the effects of 8 weeks of endurance training on coenzyme Q (Q) content and the formation of reactive oxygen species (ROS) at the tissue level and in isolated mitochondria of the rat heart, liver and brain. We demonstrated that endurance training enhanced mitochondrial biogenesis in all tested organs, while a significant increase in the Q redox state was observed in the heart and brain, indicating an elevated level of QH2 as an antioxidant. Moreover, endurance training increased the mQH2 antioxidant pool in the mitochondria of the heart and liver, but not in the brain. At the tissue and isolated mitochondria level, an increase in ROS formation was only observed in the heart. ROS formation observed in the mitochondria of individual rat tissues after training may be associated with changes in the activity/amount of individual components of the oxidative phosphorylation system and its molecular organization, as well as with the size of the oxidized pool of mitochondrial Q acting as an electron carrier in the respiratory chain. Our results indicate that tissue-dependent changes induced by endurance training in the cellular and mitochondrial QH2 pool acting as an antioxidant and in the mitochondrial Q pool serving the respiratory chain may serve important roles in energy metabolism, redox homeostasis and the level of oxidative stress.

The mTOR/PGC-1α/SIRT3 Pathway Drives Reductive Glutamine Metabolism to Reduce Oxidative Stress Caused by ISKNV in CPB Cells

Infectious spleen and kidney necrosis virus (ISKNV) is the causative agent of farmed fish disease that has caused huge economic losses in fresh and marine fish aquaculture. The redox state of cells is shaped by virus into a favorable microenvironment for virus replication and proliferation.

High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats

High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)—offspring of standard diet fed dams who received a standard diet after weaning (n = 9–11), control-HS (C-HS)—offspring of standard diet fed dams who received a HS diet after weaning (n = 9–11), HS-C—offspring of HS diet fed dams who received a standard diet after weaning (n = 9–11), and HS-HS—offspring of HS diet fed dams who received a HS diet after weaning (n = 9–11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.

Experimental Evolution Reveals Redox State Modulates Mycobacterial Pathogenicity

Understanding how Mycobacterium tuberculosis has evolved into a professional pathogen is helpful in studying its pathogenesis and for designing vaccines. We investigated how the evolutionary adaptation of M. smegmatis mc251 to an important clinical stressor H2O2 allows bacteria undergo coordinated genetic mutations, resulting in increased pathogenicity. Whole-genome sequencing identified a mutation site in the fur gene, which caused increased expression of katG. Using a Wayne dormancy model, mc251 showed a growth advantage over its parental strain mc2155 in recovering from dormancy under anaerobic conditions. Meanwhile, the high level of KatG in mc251 was accompanied by a low level of ATP, which meant that mc251 is at a low respiratory level. Additionally, the redox-related protein Rv1996 showed different phenotypes in different specific redox states in M. smegmatis mc2155, mc251, M. bovis BCG and M. tuberculosis mc27000. In conclusion, our study shows that the same gene presents different phenotypes under different physiological conditions. This may partly explain why M. smegmatis and M. tuberculosis have similar virulence factors and signaling transduction systems such as two-component systems and sigma factors, but due to the different redox states in the corresponding bacteria, M. smegmatis is a nonpathogen, while M. tuberculosis is a pathogen. As mc251 overcomes its shortcomings of rapid removal, it can be potentially developed as a vaccine vector.

The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Approximately 78% of cases are caused by mutations in the PKD1 gene, which encodes polycystin-1 (PC1). PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid residues of PC1 in a Pkd1-KO orthologous murine model of ADPKD dramatically suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase. This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.

Organic Matter Redox State Driven by Specific Sources in Mangrove Sediments: A Case Study from Peruvian Ecosystems

In order to determine the organic matter redox state in relation to specific sources in mangrove sediments, two 60 cm-long sediment cores were collected from mangrove-covered and mudflat zones within a mangrove forest in Peru. Sediment subsamples from these cores were analyzed to determine δ13C values and C:N ratios, whereas two redox indices, namely, electrochemical (fEAOM) and spectroscopical (A1650/A3400) indices, were taken from a previous study and correlated with the geochemical indices obtained from this work. These indices may provide accurate information on sedimentary organic matter diagenesis by oxidative processes through its redox state. The results show that the electrochemical index (fEAOM) and the spectroscopical index (A1650/A3400) for mangrove-covered sediments exhibited a positive correlation with δ13C values and a negative correlation with C:N molar ratios. These correlations suggest that the more labile sedimentary organic matter derived from non-terrestrial sources is in a more oxidized state than that derived from mangrove vegetation. However, this was not valid for mudflat zones, where non-significant correlations between geochemical indices were observed. Furthermore, the results suggest that the redox state of the organic matter deposited over time is dependent on source mixing influences, being better preserved in the presence of mangrove-derived organic matter.

Association Between Plasma Redox State/Mitochondria Function and a Flu-Like Syndrome/COVID-19 in the Elderly Admitted to a Long-Term Care Unit

Background/Aims: It is widely known that the imbalance between reactive oxygen species (ROS)/antioxidants and mitochondrial function could play a pivotal role in aging and in the physiopathology of viral infections. Here, we correlated the plasma oxidants/antioxidants levels of the elderly admitted to a long-term care (LTC) unit with clinical data in relation to flu-like disease/COVID-19. Moreover, in vitro we examined the effects of plasma on cell viability, ROS release and mitochondrial function.Materials and Methods: In 60 patients admitted to LTC unit for at least 1 year at moderate or high care load, demographic and clinical variables were taken. Blood samples were collected for the evaluations of oxidants/antioxidants, as thiobarbituric acid reactive substances, 8-hydroxy-2-deoxyguanosine, 8-isoprostanes, superoxide dismutase activity, glutathione, and vitamin D. In vitro, human umbilical vascular endothelial cells (HUVEC) were used to examine the effects of plasma on viability, ROS release and mitochondrial membrane potential.Results: The results obtained showed that the redox state of the elderly was quite balanced; mitochondrial membrane potential of HUVEC was reduced by about 20%, only. Also, the correlation analysis evidenced the association between mitochondrial function and the patients’ outcomes. Interestingly, lower levels of mitochondrial membrane potential were found in the elderly who had symptoms suggestive of COVID-19 or with a confirmed diagnosis of COVID-19.Conclusion: The results of this study highlight the importance of mitochondrial function in the tendency to get a flu-like syndrome like COVID-19 in the elderly admitted to LTC unit. This information could have clinical implications for the management of old population.

Mantle wedge oxidation due to sediment-infiltrated deserpentinisation

The Earth's mantle is oxygen-breathing through the ¬sink of oxidised tectonic plates at convergent margins. Ocean floor serpentinisation increases the bulk oxidation state of iron relative to dry oceanic mantle and results in a variable intake of other redox-sensitive elements such as sulphur. The reversibility of seafloor oxidation in subduction zones during high-pressure dehydration of serpentinite (“deserpentinisation”) at subarc depths and the capacity of the resulting fluids to oxidise the mantle source of arc basalts are highly contested. Thermodynamic modelling, experiments, and metaperidotite study in exhumed high-pressure terrains result in differing estimates of the redox state of deserpentinisation fluids, ranging from low to highly oxidant. Here we show that although intrinsic deserpentinisation fluids are highly oxidant, the infiltration of small fractions of external fluids equilibrated with metasedimentary rocks strongly modulates their redox state and oxidation-reduction capacity explaining the observed discrepancies in their redox state. Infiltration of fluids equilibrated with graphite-bearing sediments reduces the oxidant, intrinsic deserpentinisation fluids to oxygen fugacities similar to those observed in most graphite-furnace experiments and natural metaperidotites. However, infiltration of CO2-bearing fluids equilibrated with modern GLOSS generates sulphate-rich, highly oxidising deserpentinisation fluids. We show that such GLOSS-infiltrated deserpentinisation fluids can effectively oxidise the mantle wedge of cold to hot subduction zones potentially accounting for the presumed oxidised nature of the source of arc basalts.