Triarylmethyl-based biradical as a superoxide probe

Abstract

Superoxide radical represents one of the most biologically relevant reactive oxygen species involved in numerous physiological and pathophysiological processes. Superoxide measurement through the decay of an electron paramagnetic resonance (EPR) signal of a triarylmethyl (TAM) radical possesses the advantage of a high selectivity and relatively high rate constant of TAM reaction with the superoxide. Hereby we report a straightforward synthesis and characterization of a TAM–TAM biradical showing a high reactivity with superoxide (second-order rate constant, (6.7?±?0.2)?×?10³ M^?1 s^?1) enabling the measurement of superoxide radical by following the increase of a sharp EPR signal associated with the formation of a TAM-quinone-methide monoradical product.     

Guanine Nucleotide Exchange Factor OSG-1 Confers Functional Aging via Dysregulated Rho Signaling in Caenorhabditis elegans Neurons

Genetic studies usually focus on quantifying and understanding the existence of genetic control on expected phenotypic outcomes. However, there is compelling evidence suggesting the existence of genetic control at the level of environmental variability, with some genotypes exhibiting more stable and others more volatile performance. Understanding the mechanisms responsible for environmental variability not only informs medical questions but is relevant in evolution and in agricultural science. In this work fully sequenced inbred lines of Drosophila melanogaster were analyzed to study the nature of genetic control of environmental variance for two quantitative traits: starvation resistance (SR) and startle response (SL). The evidence for genetic control of environmental variance is compelling for both traits. Sequence information is incorporated in random regression models to study the underlying genetic signals, which are shown to be different in the two traits. Genomic variance in sexual dimorphism was found for SR but not for SL. Indeed, the proportion of variance captured by sequence information and the contribution to this variance from four chromosome segments differ between sexes in SR but not in SL. The number of studies of environmental variation, particularly in humans, is limited. The availability of full sequence information and modern computationally intensive statistical methods provides opportunities for rigorous analyses of environmental variability.     

Interplay between vitamin E and phosphorus availability in the control of longevity in Arabidopsis thaliana

Background and Aims Vitamin E helps to control the cellular redox state by reacting with singlet oxygen and preventing the propagation of lipid peroxidation in thylakoid membranes. Both plant ageing and phosphorus deficiency can trigger accumulation of reactive oxygen species, leading to damage to the photosynthetic apparatus. This study investigates how phosphorus availability and vitamin E interact in the control of plant longevity in the short-lived annual Arabidopsis thaliana.Methods The responses of tocopherol cyclase (VTE1)- and γ-tocopherol methyltransferase (VTE4)-null mutants to various levels of phosphorus availability was compared with that of wild-type plants. Longevity (time from germination to rosette death) and the time taken to pass through different developmental stages were determined, and measurements were taken of photosynthetic efficiency, pigment concentration, lipid peroxidation, vitamin E content and jasmonate content.Key Results The vte1 mutant showed accelerated senescence under control conditions, excess phosphorus and mild phosphorus deficiency, suggesting a delaying, protective effect of α-tocopherol during plant senescence. However, under severe phosphorus deficiency the lack of α-tocopherol paradoxically increased longevity in the vte1 mutant, while senescence was accelerated in wild-type plants. Reduced photoprotection in vitamin E-deficient mutants led to increased levels of defence chemicals (as indicated by jasmonate levels) under severe phosphorus starvation in the vte4 mutant and under excess phosphorus and mild phosphorus starvation in the vte1 mutant, indicating a trade-off between the capacity for photoprotection and the activation of chemical defences (jasmonate accumulation).Conclusions Vitamin E increases plant longevity under control conditions and mild phosphorus starvation, but accelerates senescence under severe phosphorus limitation. Complex interactions are revealed between phosphorus availability, vitamin E and the potential to synthesize jasmonates, suggesting a trade-off between photoprotection and the activation of chemical defences in the plants.     

Lysoglycerophospholipids in chronic inflammatory disorders: The PLA2/LPC and ATX/LPA axes

Lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), the most prominent lysoglycerophospholipids, are emerging as a novel class of inflammatory lipids, joining thromboxanes, leukotrienes and prostaglandins with which they share metabolic pathways and regulatory mechanisms. Enzymes that participate in LPC and LPA metabolism, such as the phospholipase A₂ superfamily (PLA₂) and autotaxin (ATX, ENPP2), play central roles in regulating LPC and LPA levels and consequently their actions. LPC/LPA biosynthetic pathways will be briefly presented and LPC/LPA signaling properties and their possible functions in the regulation of the immune system and chronic inflammation will be reviewed. Furthermore, implications of exacerbated LPC and/or LPA signaling in the context of chronic inflammatory diseases, namely rheumatoid arthritis, multiple sclerosis, pulmonary fibrosis and hepatitis, will be discussed. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.     

Plankton metabolism and physical forcing in a productive embayment of a large oligotrophic lake: insights from stable oxygen isotopes

1. The metabolic balance of plankton communities, commonly assessed by the photosynthesis‐to‐respiration ratio (P : R), has received much attention recently in connection with allochthonous organic subsidies to lakes, while the role of physical, climate‐related forces has received less attention. 2. Here we evaluated the effects of wind and upwelling events on plankton metabolism and the potential of stable oxygen isotopes to characterise P, R and P : R on the scales necessary to characterise properly physical forcing effects in large lakes. 3. We measured the ¹⁸O/¹⁶O ratio of dissolved oxygen and water in a large productive embayment of Lake Ontario (Hamilton Harbour, Canada) and estimated P, R and P : R from the steady state solutions of a widely accepted mass balance model, together with estimates of wind‐driven gas exchange, and compared the results with those from experimental incubations of plankton samples. 4. Estimates of P, but not R, from the isotope model were significantly correlated with bottle estimates while average P : R was similar by both methods. Closer examination of physical forcing events led to a model of how wind events induce mixing, upwelling, exchange and consequent changes in P and R. These physical forcing events were captured more by the isotope model than by the bottle estimates, as episodes of immediately increased R and decreased P : R, with a subsequent stimulation of P. 5. The oxygen isotope approach provided valuable measures of plankton metabolism and helped to characterise more effectively the substantial effects on P : R of physical forcing and, in particular, mixing and exchange events.     

Irradiated cationic mesoporphyrin induces larger damage to isolated rat liver mitochondria than the anionic form

The action of irradiated cationic Fe(III)TMPyP and anionic Fe(III)TPPS4 forms of mesoporphyrins on mitochondrial functions was investigated using experimental conditions that caused minimal effects on mitochondria in the dark. Treatment of mitochondria with 1 microM Fe(III)TMPyP for 2 min decreased the respiratory control by 3% in the dark and 28% after irradiation. Fe(III)TPPS4 (1 microM) had no significant effect on respiratory control under any of the above conditions. Both porphyrins increased the mitochondrial production of reactive oxygen species in the presence of Ca2+; however, the effect of Fe(III)TMPyP was significantly stronger. In both cases, this overproduction was associated with membrane lipid peroxidation. It was also observed that the association constant of Fe(III)TMPyP with mitochondria was 11 times higher than that of Fe(III)TPPS4. In conclusion, the damage to isolated mitochondria induced by Fe(III)TMPyP under illumination was larger than by Fe(III)TPPS4, probably because its cationic charge favors association with the mitochondrial membrane. This is supported by the decrease in the association constant of Fe(III)TMPyP with mitochondria in higher salt medium.