Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions

Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health

DISSECTION OF THE HORMETIC CURVE: ANALYSIS OF COMPONENTS AND MECHANISMS

The relationship between the dose of an effector and the biological response frequently is not described by a linear function and, moreover, in some cases the doseresponse relationship may change from positive/adverse to adverse/positive with increasing dose. This complicated relationship is called “hormesis”. This paper provides a short analysis of the concept along with a description of used approaches to characterize hormetic relationships. The whole hormetic curve can be divided into three zones: I – a lag-zone where no changes are observed with increasing dose; II – a zone where beneficial/ adverse effects are observed, and III – a zone where the effects are opposite to those seen in zone II. Some approaches are proposed to analyze the molecular components involved in the development of the hormetic character of dose-response relationships with the use of specific genetic lines or inhibitors of regulatory pathways. The discussion is then extended to suggest a new parameter (half-width of the hormetic curve at zone II) for quantitative characterization of the hormetic curve. The problems limiting progress in the development of the hormesis concept such as low reproducibility and predictability may be solved, at least partly, by deciphering the molecular mechanisms underlying the hormetic dose-effect relationship

Potential oxidative stress related targets of mitochondria-focused therapy of PTSD

Post-traumatic stress disorder (PTSD) remains a highly prevalent, under-diagnosed, and under-treated psychiatric disorder that often deteriorates over time, and is highly comorbid with major depressive disorder, suicidality, and substance use disorder. Several biomarkers have been proposed but have yet to be implemented into clinical practice. Treatments, including selective serotonin reuptake inhibitors, are efficacious in only a small number of patients, which underscores the need to develop novel, efficient treatments. Mitochondrial dysfunction resulting from chronic oxidative stress has been linked with both altered neurotransmitter signaling and the inflammatory response. Hereinafter, we discuss mechanisms by which mitochondrial dysfunction may contribute to the development of PTSD symptoms, and how these may even increase PTSD susceptibility. We also highlight possible therapeutic targets to reduce oxidative stress to prevent or treat PTSD symptoms

CONCENTRATION-DEPENDENT EFFECTS OF RHODIOLA ROSEA ON LONGTERM SURVIVAL AND STRESS RESISTANCE OF YEAST SACCHAROMYCES CEREVISIAE: THE INVOLVEMENT OF YAP 1 AND MSN2/4 REGULATORY PROTEINS

Concentration-dependent effects of aqueous extract from R. rosea root on long-term survival and stress resistance of budding yeast Saccharomyces cerevisiae were studied. At low concentrations, R. rosea aqueous extract extended yeast chronological lifespan, enhanced oxidative stress resistance of stationary-phase cells and resistance to number stressors in exponentially growing cultures. At high concentrations, R. rosea extract sensitized yeast cells to stresses and shortened yeast lifespan. These biphasic concentration-responses describe a common hormetic phenomenon characterized by a low-dose stimulation and a high-dose inhibition. Yeast pretreatment with low doses of R. rosea extract enhanced yeast survival and prevented protein oxidation under H2O2-induced oxidative stress. Positive effect of R. rosea extract on yeast survival under heat shock exposure was not accompanied with changes in antioxidant enzyme activities and levels of oxidized proteins. The deficiency in transcriptional regulators, Msn2/Msn4 and Yap1, abolished the positive effect of low doses of R. rosea extract on yeast viability under stress challenges. Potential involvement of Msn2/Msn4 and Yap1 regulatory proteins in realization of R. rosea beneficial effects is discussed

Effect of light emitted by diodes on growth and pigment content of black currant plantlets in vitro

The effects of cool white, natural white, and warm white lights, which have a continuous spectrum throughout the region of surfactant, and blue-red light spectrum on in vitro growth and development of black currant (Ribes nigrum L.) was studied. It was demonstrated that the spectral composition of light affected length and fresh mass of shoots and roots as well as concentrations of chlorophylls, carotenoids, and anthocyanins. The plants grown under warm white light had the longest shoots (2.5 ± 0.2 cm) and fresh mass of shoots (166 ± 12 mg) and roots (80 ± 16 mg) relatively to оne’s grown under other light types. Under blue-red and warm white lights black currant leaves possessed the highest concentrations of chlorophyll a (2.66 ± 0.31 and 2.17 ± 0.14 µmol·gwm-1, respectively), chlorophyll b (1.15 ± 0.15 and 0.87± 0.05 µmol·gwm-1), carotenoids (0.89 ± 0.09 and 0.78 ± 0.05 µmol·gwm-1, respectively) and anthocyanins (1.37 ± 0.20 and 1.09 ± 0.05 µmol·gwm-1, respectively). Thus, blue-red (B:R = 1:4) and warm white lights may be used as an alternative light source for upland black currant culture systems