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

Pdr12p-dependent and -independent fluorescein extrusion from baker's yeast cells

Fluorescein efflux from S. cerevisiae cells was measured to study the peculiarities of fluorescein transport system, which is important for yeast resistance to certain drugs and weak organic acid preservatives. Glucose-independent and glucose-stimulated fluorescein effluxes were characterized using iodoacetate, cyanide and orthovanadate, inhibitors of glycolysis, electron transport chain, and ATPases, respectively. It is supposed that in glucose-free medium fluorescein extrusion is ATP-dependent and the energy for this efflux is mainly provided by respiration. In glucose-containing medium, glycolysis plays a critical role for extrusion of fluorescein. The results indicate that acetic acid inhibits the fluorescein efflux from yeast cells. The inhibition constant of glucose-stimulated fluorescein efflux is significantly lower in parental strain than in two mutants defective in PDR12 (ABC-transporter Pdr12p) or WAR1 (transcription factor of Pdr12p). It can be suggested that the membrane protein Pdr12 is involved in fluorescein extrusion from the yeast cells, but component(s) other than Pdr12p is (are) also important

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