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

Effects of alpha-ketoglutarate on lifespan and functional aging of Drosophila melanogaster flies

The effects of an alpha-ketoglutarate-supplemented diet on lifespan and functional senescence were evaluated in the Canton S strain of Drosophila melanogaster. The results suggest that effects of dietary alpha-ketoglutarate (AKG) are dose- and gender-dependent. In males, diets containing 1-10 mM AKG did not affect mean and maximum lifespans, except that an increased maximum lifespan observed at 10 mM AKG. Diet with 20 mM AKG shortened median lifespan and had no effect on maximum lifespan of males. In females, diets with low concentrations of AKG (1 and 5 mM) did not affect lifespan, whereas diets supplemented with 10 and 20 mM AKG increased both median and maximum lifespans. At a lifespan-prolonging concentration (10 mM), AKG decreased fecundity, increased cold resistance and had no effect on climbing activity or resistance to oxi­dative stress in flies of either gender at middle (24 days) and old (40 days) ages. Moreover, middle-aged AKG-fed females but not males were more resistant to heat stress that was accompanied by higher levels of HSP90 protein as compared with controls. Middle-aged flies on AKG-supplemented diets showed elevated oxidative stress and had higher total protein and triacylglycerol levels as compared with controls. Hence, anti-aging effects of AKG do not seem to be related to preventing oxidative stress development but involve metabolic rearrangement and synthesis of specific protective proteins, which aid to resist destructive processes with age

Intermittent fasting causes metabolic stress and leucopenia in young mice

Overweight and obesity became the worldwide epidemic resulting from overeating especially when a so-called Western diet rich in carbohydrates and fats is used. It is widely accepted that limitation of food consumption could help to withstand such state of adult organism, but information about younger groups is contradictory. The present study was undertaken to characterize the effects of intermittent fasting, using an every other day (EOD) fasting/feeding protocol, on hematological parameters and biochemical blood plasma indices in young mice from one to two months old. It was shown that intermittently fasted mice were characterized by a reduced body weight, reduced total number of blood leucocytes, lower glucose and lactate levels and higher activity of alanine aminotransferase and aspartate aminotransferase in blood plasma as compared with the age-matched control mice. To gain the same mass EOD animals needed to eat more food than ad libitum fed animals. These differences may probably be explained by a need to expend certain resources to combat stress induced by intermittent fasting. Our data showed that EOD feeding at a young age may negatively influence young mammals

Comparison of Yarrowia lipolytica and Pichia pastoris cellular response to different agents of oxidative stress

Yeast cells exposed to adverse conditions employ a number of defense mechanisms in order to respond effectively to the stress effects of reactive oxygen species. In this work, the cellular response of Yarrowia lipolytica and Pichia pastoris to the exposure to the ROSinducing agents’ paraquat, hydrogen peroxide, and increased air pressure was analyzed. Yeast cells at exponential phase were exposed for 3 h to 1 mM paraquat, to 50 mM H2O2, or to increased air pressure of 3 or 5 bar. For both strains, the cellular viability loss and lipid peroxidation was lower for the cells exposed to increased air pressure than for those exposed to chemical oxidants. The glutathione induction occurred only in Y. lipolytica strain and reached the highest level as a response to PQ exposure. In general, antioxidant enzymes were more expressed in Y. lipolytica than in P. pastoris. The enzyme superoxide dismutase was induced in both strains under all the oxidant conditions but was dependent on the cellular growth phase, being undetectable in non-growing cells, whereas glutathione reductase was more induced in those conditions. Hydrogen peroxide was the most efficient inducer of catalase. Both yeast cultures underwent no cellular growth inhibition with increased air pressure, indicating that these yeast species were able to adapt to the oxidative stressful environment.The authors acknowledge the financial support provided by "Fundacao para a Ciencia e Tecnologia" (Grant SFRH/BD/47371/2008)

Effects of bicarbonate and alpha-ketoglutarate on sensitivity of Saccharomyces cerevisiae yeast to hydrogen peroxide and iron ions

The effects of sodium bicarbonate on the sensitivity of Saccharomyces cerevisiae yeast to hydrogen peroxide and ferrous sulfate were studied. Viability of yeast cells treated with 10–25 mM H2O2 and 0.1–0.2 mM FeSO4 was significantly decreased when 25 or 50 mM NaHCO3 was added to the medium. In the absence of bicarbonate, the levels of oxidative stress markers, namely protein carbonyls, total and oxidized glutathione in cells exposed to 0.2 mM FeSO4 did not differ from such levels in control cells (without FeSO4). Yeast cells incubated with 0.2 mM FeSO4 and 50 mM NaHCO3 had similar levels of oxidized glutathione and carbonyl groups in proteins but lower level of total glutathione compared to cells treated with FeSO4 in the absence of NaHCO3. Yeast cells exposed to a mixture of “2 mM H2O2 + 2 mM FeSO4” in 50 mM sodium bicarbonate buffer survived better than cells treated with these oxidants in 50 mM potassium phosphate buffer. The addition of 10 mM alpha-ketoglutarate led to the increased yeast survival in both buffers under the treatment with “Fe2+/Н2О2”. The protective effect of alpha-ketoglutarate can be due to its H2O2-scavenging activity. The results suggest that bicarbonate ions can enhance or alleviate the toxic effects of redox-active compounds on S. cerevisiae. Pro/antioxidant effects of bicarbonate ions are likely to depend on the kinetics of interaction between HCO3ˉ and produced ROS

Homeostasis of carbohydrates and reactive oxygen species is critically changed in the brain of middle-aged mice: Molecular mechanisms and functional reasons

The brain is an organ that consumes a lot of energy. In the brain, energy is required for synaptic transmission, numerous biosynthetic processes and axonal transport in neurons, and for many supportive functions of glial cells. The main source of energy in the brain is glucose and to a lesser extent lactate and ketone bodies. ATP is formed at glucose catabolism via glycolysis and oxidative phosphorylation in mitochondrial electron transport chain (ETC) within mitochondria being the main source of ATP. With age, brain's energy metabolism is disturbed, involving a decrease in glycolysis and mitochondrial dysfunction. The latter is accompanied by intensified generation of reactive oxygen species (ROS) in ETC leading to oxidative stress. Recently, we have found that crucial changes in energy metabolism and intensity of oxidative stress in the mouse brain occur in middle age with minor progression in old age. In this review, we analyze the metabolic changes and functional causes that lead to these changes in the aging brain

Chromium(VI) Toxicity in Legume Plants: Modulation Effects of Rhizobial Symbiosis

Most legume species have the ability to establish a symbiotic relationship with soil nitrogen-fixing rhizobacteria that promote plant growth and productivity. There is an increasing evidence of reactive oxygen species (ROS) important role in formation of legume-rhizobium symbiosis and nodule functioning. Environmental pollutants such as chromium compounds can cause damage to rhizobia, legumes, and their symbiosis. In plants, toxic effects of chromium(VI) compounds are associated with the increased production of ROS and oxidative stress development as well as with inhibition of pigment synthesis and modification of virtually all cellular components. These metabolic changes result in inhibition of seed germination and seedling development as well as reduction of plant biomass and crop yield. However, if plants establish symbiosis with rhizobia, heavy metals are accumulated preferentially in nodules decreasing the toxicity of metals to the host plant. This review summarizes data on toxic effects of chromium on legume plants and legume-rhizobium symbiosis. In addition, we discussed the role of oxidative stress in both chromium toxicity and formation of rhizobial symbiosis and use of nodule bacteria for minimizing toxic effects of chromium on plants

Concentration-Dependent Effects of on Long-Term Survival and Stress Resistance of Yeast : 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 H 2 O 2 -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