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At least 505 records · Page 28

Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System

Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA’s Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss.

60 APPLIED LIFE SCIENCES↗

Cu Homeostasis in Bacteria: The Ins and Outs

Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for cuproprotein biogenesis with the need to remove excess Cu. This review summarizes our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative bacteria and describes the multiple strategies that bacteria use for uptake, storage and export of Cu. We furthermore describe general mechanistic principles that aid the bacterial response to toxic Cu concentrations and illustrate dedicated Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu quota for cell proliferation is of particular importance for microbial pathogens because Cu is utilized by the host immune system for attenuating pathogen survival in host cells.

36 MATERIALS SCIENCE↗

Melanoxetin: A Hydroxylated Flavonoid Attenuates Oxidative Stress and Modulates Insulin Resistance and Glycation Pathways in an Animal Model of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin’s therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

Rocha, Sónia (ORCID:0000000177862731)↗

Transcriptional Suppression of Renal Antioxidant Enzyme Systems in Guinea Pigs Exposed to Polymerized Cell-Free Hemoglobin

Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury has raised safety concerns. Using a guinea pig exchange transfusion model, we examined the effects of polymerized bovine hemoglobin (HbG) on the transcriptional regulation, activity, and expression of the renal antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). HbG infusion downregulated the mRNA levels for genes encoding SOD isoforms 1-3, GPx1, GPx3, GPx4, and CAT. This transcriptional suppression correlated with decreased enzymatic activities for SOD, CAT, and GPx. Immunostaining revealed decreased protein expression of SOD1, CAT, and GPx1 primarily in renal cortical tubules. DNA methylation analyses identified CpG hypermethylation in the gene promoters for SOD1-3, GPx1, GPx3, and GPx4, suggesting an epigenetic-based mechanism underlying the observed gene repression. HbG also induced oxidative stress as evidenced by increased renal lipid peroxidation end-products and 4-HNE immunostaining, which could be the result of the depleted antioxidant defenses and/or serve as a trigger for increased DNA methylation. Together, these findings provide evidence that the renal exposure to HbG suppresses the function of major antioxidant defense systems which may have relevant implications for understanding the safety of hemoglobin-based products.

DNA methylation↗

Nanomaterials in Biomedicine

Nowadays, nanomaterials have become an emerging field that has shown great promise in the development of novel diagnostic, imaging and therapeutic agents for a variety of diseases, including cancer, due to their nanoscale size effects and increased surface area. In comparison to their larger counterparts, nanomaterials have unique physicochemical and biological properties including size, shape, chemical composition, surface structure and charge, aggregation and agglomeration, and solubility which can affect their interactions with biomolecules and cells. In addition, nanoparticles (NPs) with size-tunable light emission have demonstrated an impressive potential as high-efficiency delivery transporters for biomolecules into cells, being used to produce exceptional images of tumor sites. Moreover, NPs delivery system has been widely applied in pharmaceutical field to enhance absorption of bioactive compounds since they can interact with several phytochemicals by hydrogen bonds and hydrophobic interactions to encapsulate these phytochemicals in NPs and thus enhance aqueous solubility of the chemicals. Moreover, NPs also can prevent against oxidation/degradation of the phytochemicals encapsulated in the gastrointestinal tract and can be taken directly up by epithelial cells in the small intestine resulting in the increase of absorption and bioavailability of phytochemicals. In general, there are two specific fields of utilization of intrinsically active NPs as pharmacologic agents including oxidative-related pathologies and cancer. On the other hand, Redox active NPs have been shown to ameliorate many clinically relevant pathological disorders that implicate oxidative stress, reducing the oxidative burden and alleviating many important symptoms. In additionuch NPs act either in a catalytic way resembling the action of antioxidant enzymes such as catalase and superoxide dismutase, or as activating surfaces to facilitate reactions between the aqueous environment and the reactive oxygen species present at high level in the pathological tissues. In anticancer therapies, metal and metal oxide NPs are being used experimentally to directly kill tumor cells e.g., allowing extremely localized thermoablation by transforming applied magnetic fields into strong hyperthermia, or performing efficient photodynamic therapies able to reach even the internal tissues by transforming a penetrating infrared radiation into visible light inside the tumor. Moreover, NPs made of heavy atoms are able to react to irradiation producing cytocidal reactive oxygen species, consequently increasing the proapototic effects of radiotherapies once correctly localized at the site of the tumor. One of the most important applications of NPs in medicine is the controlled drug release. Sustained (or continuous) release drug delivery system involves NPs that release drugs at a controlled rate, by diffusion or degradation of the structure of the nanoparticle over time]. Other nano drug delivery approaches are focused on crossing certain physical barriers, such as the blood-brain barrier, or on finding alternative and acceptable routes for the delivery of a new generation of drugs based on proteins to be used through the gastrointestinal tract and prevent degradation. However, a successful system for the transfer of drugs needs to demonstrate optimal drug loading and good qualities of its release, a long duration in storage and low toxicity. On the other hand, carbon-based nanostructured materials, such as graphene, carbon nanotubes (CNTs) and nanodiamonds (NDs), have demonstrated to be highly promising materials for designing and fabricating nanoelectrodes and substrates for cell growth, by virtue of their peerless optical, electrical, thermal and mechanical properties. Nanoscience and nanotechnology are the basis of innovative and unprecedented techniques, offering unimaginable potential for the benefit of patients and new markets, companies that manufacture pharmaceuticals, and drug delivery systems.

59 BASIC BIOLOGICAL SCIENCES↗

Zymomonas mobilis oxidative stress transcriptomics

Zymomonas mobilis is an important bioenergy organism that has potential to produce biofuels, including ethanol, in high volumes. Here we examined the response of Zymomonas mobilis to various oxidative stresses using genome-scale transcriptomics data. We first examined the transcrpit abundance in WT aerobic growth compared to aerobic grown in paraquat, which forms superoxide. Under anaerobic growth conditions we compared WT Zymomonas mobilis with strains grown in media lacking iron as well as strains lacking iron that were treated with the iron chelator DIP before collection. Finally we examined transcript abundance in cells lacking ZMO_0422 (Rrf2 family transcription factor homolog) and ZMO_1411 (Fur homolog) grown under anaerobic conditions. Overall design: Transcriptomic analysis of WT, a deletion of ZMO_0422, and a deletion of ZMO_1411 in Zymomonas mobilis ZM4 under aerobic and anaerobic growth conditions along with various oxidative stresses: Paraquate addition, No Iron, and hydrogen peroxide addition.

aerobic↗

Engineering aspects of the experiment and results of animal tests

A closed passive system independent of support from the spacecraft or its crew was developed to house five pocket mice for their flight on Apollo XVII. The reaction of potassium superoxide with carbon dioxide and water vapor to produce oxygen provided a habitable atmosphere within the experiment package. The performance of the system and the ability of the mice to survive the key preflight tests gave reasonable assurance that the mice would also withstand the Apollo flight.-

Look, B. C.↗

Possible surface reactions on Mars - Implications for Viking biology results

The results of two of the three biology experiments carried out on the Viking Mars landers have been simulated. The mixture of organic compounds labeled with carbon-14 used on Mars released carbon dioxide containing carbon-14 when reacted with a simulated Martian surface and atmosphere exposed to ultraviolet light (labeled release experiment). Oxygen was released when metal peroxides or superoxides were treated with water (gas exchange experiment). The simulations suggest that the results of these two Viking experiments can be explained on the basis of reactions of the Martian surface and atmosphere.

Ponnamperuma, C.↗

Process for preparing higher oxides of the alkali and alkaline earth metals

High purity inorganic higher oxides of the alkali and alkaline earth metals are prepared by subjecting the hydroxide of the alkali and alkaline earth metal to a radio frequency discharge sustained in oxygen. The process is particulary adaptable to the production of high purity potassium superoxide by subjecting potassium hydroxide to glow discharge sustained in oxygen under the pressure of about 0.75 to 1.00 torr.

Sadhukhan, P.↗

The Viking gas exchange experiment results from Chryse and Utopia surface samples

Immediate gas changes occurred when untreated Martian surface samples were humidified and/or wet by an aqueous nutrient medium in the Viking lander gas exchange experiment. The evolutions of N2, CO2, and Ar are mainly associated with soil surface desorption caused by water vapor, while O2 evolution is primarily associated with decomposition of superoxides inferred to be present on Mars. On recharges with fresh nutrient and test gas, only CO2 was given off, and its rate of evolution decreased with each recharge. This CO2 evolution is thought to come from the oxidation of organics present in the nutrient by gamma Fe2O3 in the surface samples. Atmospheric analyses were also performed at both sites. The mean atmospheric composition from four analyses is N2, 2.3%; O2, not greater than 0.15%; Ar, 1.5% and CO2, 96.2%.

Oyama, V. I.↗

Chemical interpretation of Viking Lander 1 life detection experiment

An earth-based evaluation of the Viking Lander 1 life-detection experiments was conducted using a radiofrequency glow discharge in a simulated Martian atmosphere. The Gas Exchange Experiment conducted in the humid mode released substantial amounts of CO2, O2, N2, Ar, and CO into the atmosphere, indicating that these substances were adsorbed onto the Martian soil. An adsorption potential plot is given, graphing quantity of gas against time (d). For a model surface area of 17 squares meters per gram of measured substance, oxygen adsorption was found to be relatively high, a result which tends to confirm the hypothesis that Martian oxygen exists largely in chemisorbed states or in active oxygen compounds, e.g., peroxide, superoxide, hydroperoxide

Ballou, E. V.↗

Analysis and interpretation of Viking labeled release experimental results

The Viking Labeled Release (LR) life detection experiment on the surface of Mars produced data consistent with a biological interpretation. In considering the plausibility of this interpretation, terrestrial life forms were identified which could serve as models for Martian microbial life. Prominent among these models are lichens which are known to survive for years in a state of cryptobiosis, to grow in hostile polar environments, to exist on atmospheric nitrogen as sole nitrogen source, and to survive without liquid water by absorbing water directly from the atmosphere. Another model is derived from the endolithic bacteria found in the dry Antarctic valleys; preliminary experiments conducted with samples of these bacteria indicate that they produce positive LR responses approximating the Mars results. However, because of the hositility of the Martian environment to life, and the failure to find organics on the surface of Mars, a number of nonbiological explanations were advanced to account for the Viking LR data. A reaction of the LR nutrient with putative surface hydrogen peroxide is the leading candidate. Other possibilities raised include reactions caused by or with ultraviolet irradiation, gamma-Fe2O3, metalloperoxides or superoxides.

Levin, G. V.↗

A model of Martian surface chemistry

Alkaline earth and alkali metal superoxides and peroxides, gamma-Fe2O3 and carbon suboxide polymer, are proposed to be constituents of the Martian surface material. These reactive substances explain the water modified reactions and thermal behaviors of the Martian samples demonstrated by all of the Viking Biology Experiments. It is also proposed that the syntheses of these substances result mainly from electrical discharges between wind-mobilized particles at Martian pressures; plasmas are initiated and maintained by these discharges. Active species in the plasma either combine to form or react with inorganic surfaces to create the reactive constituents.

Oyama, V. I.↗

Chemistry of peroxide compounds

The history of Soviet research from 1866 to 1967 on peroxide compounds is reviewed. This research dealt mainly with peroxide kinetics, reactivity and characteristics, peroxide production processes, and more recently with superoxides and ozonides and emphasis on the higher oxides of group 1 and 2 elements. Solid state fluidized bed synthesis and production of high purity products based on the relative solubilities of the initial, intermediate, and final compounds and elements in liquid ammonia are discussed.

Volnov, I. I.↗

Use of glow discharge in fluidized beds

Static charges and agglomerization of particles in a fluidized bed systems are minimized by maintaining in at least part of the bed a radio frequency glow discharge. This approach is eminently suitable for processes in which the conventional charge removing agents, i.e., moisture or conductive particle coatings, cannot be used. The technique is applied here to the disproportionation of calcium peroxide diperoxyhydrate to yield calcium superoxide, an exceptionally water and heat sensitive reaction.

Wydeven, T.↗

Is cell aging caused by respiration-dependent injury to the mitochondrial genome

Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article, the hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells is expanded. It is maintained that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and, therefore, of organismic performance.

Fleming, J. E.↗

Differential effect of denervation on free radical scavenging enzymes in slow and fast muscle of rat

To determine the effect of denervation on the free radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the mid-thigh region and the muscle tissue levels of 5 enzymes were studied 2 and 5 weeks following crush. Radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. These data represent the first systematic report of free radical scavening systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle.

Asayama, K.↗