Exhaustive Exercise Increases Spontaneous but Not fMLP-Induced Production of Reactive Oxygen Species by Circulating Phagocytes in Amateur Sportsmen

Strenuous exercise alters the oxidative response of blood phagocytes to various agonists. However, little is known about spontaneous post exercise oxidant production by these cells. In this cross-over trial, we tested whether an exhaustive treadmill run at a speed corresponding to 70% of VO2max affects spontaneous and fMLP-provoked oxidant production by phagocytes in 18 amateur sportsmen. Blood was collected before, just after, and 1, 3, 5 and 24 h post exercise for determination of absolute and normalized per phagocyte count spontaneous (a-rLBCL, rLBCL) and fMLP-induced luminol-enhanced whole blood chemiluminescence (a-fMLP-LBCL, fMLP-LBCL). a-rLBCL and rLBCL increased by 2.5- and 1.5-times just after exercise (p < 0.05) and then returned to baseline or decreased by about 2-times at the remaining time-points, respectively. a-fMLP-LBCL increased 1.7- and 1.6-times just after and at 3 h post-exercise (p < 0.05), respectively, while fMLP-LBCL was suppressed by 1.5- to 2.3-times at 1, 3, 5 and 24 h post-exercise. No correlations were found between elevated post-exercise a-rLBCL, a-fMLP-LBCL and run distance to exhaustion. No changes of oxidants production were observed in the control arm (1 h resting instead of exercise). Exhaustive exercise decreased the blood phagocyte-specific oxidative response to fMLP while increasing transiently spontaneous oxidant generation, which could be a factor inducing secondary rise in antioxidant enzymes activity.

Empowering Melatonin Therapeutics with Drosophila Models

Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases.

Fruit Herbivory Alters Plant Electrome: Evidence for Fruit-Shoot Long-Distance Electrical Signaling in Tomato Plants

The electrical activity of tomato plants subjected to fruit herbivory was investigated. The study aimed to test the hypothesis that tomato fruits transmit long-distance electrical signals to the shoot when subjected to herbivory. For such, time series classification by machine learning techniques and analyses related to the oxidative response were employed. Tomato plants (cv. “Micro-Tom”) were placed into a Faraday's cage and an electrode pair was inserted in the fruit's peduncle. Helicoverpa armigera caterpillars were placed on the fruit (either green and ripe) for 24 h. The time series were recorded before and after the fruit's exposure of the caterpillars. The plant material for chemical analyses was collected 24 and 48 h after the end of the acquisition of electrophysiological data. The time series were analyzed by the following techniques: Fast Fourier Transform (FFT), Wavelet Transform, Power Spectral Density (PSD), and Approximate Entropy. The following features from FFT, PSD, and Wavelet Transform were used for PCA (Principal Component Analysis): average, maximum and minimum value, variance, skewness, and kurtosis. Additionally, these features were used in Machine Learning (ML) analyses for looking for classifiable patterns between tomato plants before and after fruit herbivory. Also, we compared the electrome before and after herbivory in the green and ripe fruits. To evaluate an oxidative response in different organs, hydrogen peroxide, superoxide anion, catalase, ascorbate peroxidase, guaiacol peroxidase, and superoxide dismutase activity were evaluated in fruit and leaves. The results show with 90% of accuracy that the electrome registered in the fruit's peduncle before herbivory is different from the electrome during predation on the fruits. Interestingly, there was also a sharp difference in the electrome of the green and ripe fruits' peduncles before, but not during, the herbivory, which demonstrates that the signals generated by the herbivory stand over the others. Biochemical analysis showed that herbivory in the fruit triggered an oxidative response in other parts of the plant. Here, we demonstrate that the fruit perceives biotic stimuli and transmits electrical signals to the shoot of tomato plants. This study raises new possibilities for studies involving electrical signals in signaling and systemic response, as well as for the applicability of ML to classify electrophysiological data and its use in early diagnosis.

The copper chaperone CcsA coupling with superoxide dismutase SodA mediates oxidative stress response in Aspergillus fumigatus

Superoxide dismutases (SODs) are important metalloenzymes that protect fungal pathogens against the toxic effects of reactive oxygen species (ROS) generated by host defense mechanisms during the infection process. The activation of Cu/Zn-SOD1 is found to be dependent on its c haperone Ccs1 ( c opper c haperone for S OD1). However, the role of Ccs1 ortholog in the human pathogen Aspergillus fumigatus and how these SODs coordinate to mediate oxidative stress response remain elusive. Here, we demonstrated that A. fumigatus CcsA, a Saccharomyces cerevisiae Ccs1 ortholog, is required for cells in response to oxidative response and the activation of Sod1. Deletion of ccsA resulted in increased ROS accumulation and enhanced sensitivity to oxidative stress due to loss of SodA activity. Molecular characterization of CcsA revealed that the conserved CXC motif is required not only for the physical interaction with SodA but also for the oxidative stress adaption. Notably, addition of Mn 2+ or overexpression of cytoplasmic Mn-SodC could rescue the defects of the ccsA or sodA deletion mutant, indicating the important role of Mn 2+ and Mn-SodC in ROS detoxification; however, deletion of CcsA-SodA complex could not affect A. fumigatus virulence. Collectively, our findings demonstrate that CcsA functions as a Cu/Zn-Sod1 chaperone that participates in the adaptation to oxidative stress in A. fumigatus and provide a better understanding of the CcsA-SodA complex-mediated oxidative stress response in filamentous fungi. IMPORTANCE Reactive oxygen species (ROS) produced by phagocytes have been reported to participate in the killing of fungal pathogens. Superoxide dismutases (SODs) are considered to be the first defense line against superoxide anions. Characterizing the regulatory mechanisms of SOD activation is important for understanding how fungi adapt to oxidative stress in hosts. Our findings demonstrated that CcsA functions as a SodA chaperone in A. fumigatus and that the conserved CXC motif within CcsA is required for its interaction with SodA and the CcsA-SodA-mediated oxidative response. These data may provide new insights into how fungal pathogens adapt to oxidative stress via the CcsA-SodA complex.