Rb1 protects endothelial cells from hydrogen peroxide-induced cell senescence by modulating redox status

Objectives Endothelial senescence has been proposed to be involved in endothelial dysfunction and atherogenesis. This study investigates the effects of ginsenoside Rbl, a major constituent of ginseng,on H2O2-induced endothelial senescence.Methods Primary human umbilical vein endothelial cells（HUVECs） senescence was induced by H2O2 as judged by senescence-associated P-galactosidase assay （SA-P-gal）.Fntracellur superoxide dismutase（S0D1） activity and malondialdehyde（MDA） level were determined by commercial kit.S0D1 mRNA and protein expression were analyzed by real time PCR and Western blot.Reactive oxygen species（ROS） were determined by flow cytometry.Results Rb1 was found to reverse endothelial senescence,as witnessed by a significant decrease of senescent cell numbers. Rbl could markedly increase intracellular SOD activity, decrease the MDA level,and suppress the generation of intracellular ROS in H2O2-treated HUVECs.Consistent with these findings,Rbl can effectively restore SOD1 mRNA and protein expression which decreased in H2O2 treated cells. Conclusions Our report demonstrates thatRbl can exert reversal effects on H2O2-induced cellular senescence through modulating cellular redox status.

Elevated peroxidative glutathione redox status in atherosclerotic patients with increased thickness of carotid intima media

Background Atherosclerosis is a chronic inflammatory disease. Accumulated evidences suggest a deep involvement of oxidative damage in the development of atherosclerosis, but little is discussed over the relationship between plasma glutathione redox status as the most important intrinsic antioxidant defensive mechanism and the atherosclerosis. Methods A total of 132 patients suspected with atherosclerosis were assigned to three groups by high frequency ultrasonic examination of the carotid artery. With the thickness of intima of the carotid artery as an index of degree of atherosclerosis progression, 56 were included in plaque-forming group （A）, 42 in carotid artery intima-thickening group （B）, and 34 in normal carotid artery intima-thickness group （C）. All patients were subjected to the measurement of plasma glutathione （GSH） （reduced form GSH and oxidized form GSSG）, nicotinamide adenine dinucleotide phosphate （NADP） （reduced form NADPH and oxidized form NADP^＋）, oxidized low density lipoprotein （oxLDL）, and malondialdehyde （MDA） The GSH/GSSG and NADPH/NADP^＋ redox potentials were calculated according to the Nernst equation, and their correlation with intima thickness and oxLDL was analyzed. Results With the thickening of artery intima （from group C to A）, GSH concentration and the ratio of GSH/GSSG gradually reduced, and GSSG and GSH/GSSG redox potential gradually increased （more positive） （P 〈0.05）. The NADPH and NADPH/NADP^＋ redox status also showed similar but milder changes. The products of oxidative stress oxLDL and MDA increased significantly along with the thickening of artery intima （P 〈0.05）. The analysis of the relationship between GSH/GSSG redox potential, intima thickness, and oxLDL showed positive correlations （P 〈0.05）. The plasma GSH/GSSG redox status was positively correlated with the intima thickness of the carotid artery and the oxidized injury of LDL. The redox status shifted to oxidizing direction along with the intima thickening and plaque-forming. Conclusion Elevated peroxidative glutathione redox status was deeply implicated in atherosclerosis progressing, and it may be a sensitive and reliable index for monitoring oxidative status in atherosclerosis.

Dietary N-carbamylglutamate and L-arginine supplementation improves redox status and suppresses apoptosis in the colon of intrauterine growth-retarded suckling lambs

Previous studies have revealed that dietary N-carbamylglutamate(NCG)or L-arginine(Arg)improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation(IUGR).Whether these nutrients alter redox status and apoptosis in the colon of IUGR lambs is still unknown.This study,therefore,aimed at investigating whether dietary supplementation of Arg or NCG alters colonic redox status,apoptosis and endoplasmic reticulum(ER)stress and the underlying mechanism of these alterations in IUGR suckling Hu lambs.Forty-eight 7-d old Hu lambs,including 12 with normal birth weight(4.25±0.14 kg)and 36 with IUGR(3.01±0.12 kg),were assigned to 4 treatment groups(n=12 each;6 males and 6 females)for 3 weeks.The treatment groups were control(CON),IUGR,IUGR+Arg and IUGR+NCG.Relative to IUGR lambs,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)content,as well as proliferation index,were higher(P<0.05)whereas reactive oxygen species(ROS),malondialdehyde(MDA)levels and apoptotic cell numbers were lower(P<0.05)in colonic tissue for both IUGR+Arg and NCG lambs.Both m RNA and protein levels of C/EBP homologous protein 10(CHOP10),B-cell lymphoma/leukaemia 2(Bcl-2)-associated X protein(Bax),apoptosis antigen 1(Fas),activating transcription factor 6(ATF6),caspase 3,and glucose-regulated protein 78(GRP78)were lower(P<0.05)while glutathione peroxidase 1(GPx1),Bcl-2 and catalase(CAT)levels were higher(P<0.05)in colonic tissue for IUGR+Arg and IUGR+NCG lambs compared with IUGR lambs.Based on our results,dietary NCG or Arg supplementation can improve colonic redox status and suppress apoptosis via death receptor-dependent,mitochondrial and ER stress pathways in IUGR suckling lambs.

Dietary dimethylglycine sodium salt supplementation alleviates redox status imbalance and intestinal dysfunction in weaned piglets with intrauterine growth restriction

There are few studies on the mechanism of redox status imbalance and intestinal dysfunction in intrauterine growth restricted(IUGR)newborn piglets.Here,we investigated the mechanism of jejunum dysfunction in weaned piglets with IUGR and the mechanism through which dimethylglycine sodium salt(DMG-Na)supplementation improving the imbalance of their redox status.In this work,a total of 10 normal birth weight(NBW)newborn piglets and 20 IUGR newborn piglets were obtained.After weaning at 21 d,they were assigned to 3 groups(n=10/group):NBW weaned piglets fed standard basal diets(NBWC);one IUGR weaned piglets fed standard basal diets(IUGRC);another IUGR weaned piglets from the same litter fed standard basal diets plus 0.1%DMG-Na(IUGRD).The piglets in these 3 groups were sacrificed at 49 d of age,and the blood and jejunum samples were collected immediately.The growth performance values in the IUGRC group were lower(P<0.05)than those in the NBWC group.Jejunum histomorphological parameters,inflammatory cytokines,and digestive enzyme activity as well as serum immunoglobulin were lower(P<0.05)in the IUGRC group than those in the NBWC group.Compared with these in the NBWC group,the redox status of serum,jejunum,and mitochondria and the expression levels of jejunum redox status-related,cell adhesion-related,and mitochondrial function-related genes and proteins were suppressed in the IUGRC group(P<0.05).However,compared with those in the IUGRC group,the growth performance values,jejunum histomorphological parameters,inflammatory cytokines,digestive enzyme activity,serum immunoglobulin,redox status of serum,jejunum,and mitochondria,and the expression levels of jejunum redox status-related,cell adhesion-related,and mitochondrial function-related genes and proteins were improved(P<0.05)in the IUGRD group.In conclusion,dietary DMG-Na supplementation alleviates redox status imbalance and intestinal dysfunction in IUGR weaned piglets mainly by activating the sirtuin 1(SIRT1)/peroxisome proliferatoractivated receptorgcoactivator-1a(PGC1a)pathway,thereby improving their unfavorable body state.

Relation of tea ingestion to salivary redox and flow rate in healthy subjects

The biochemistry of human saliva can be altered by food intake.The benefits of tea drinking were extensively studied but the influence of tea ingestion on human saliva has not been revealed.The work aimed to investigate the immediate and delayed effect of vine tea,oolong tea and black tea intake on certain salivary biochemistry and flow rate.The saliva samples of healthy subjects were collected before,after and 30 min after tea ingestion.The chemical compositions and antioxidant capacity of tea samples were analyzed to correlate with salivary parameters.Principal component analysis indicated that the effects of vine tea consumption were dominated by increasing salivary flow rate(SFR),production rate of total protein(TPC),thiol(SH),malondialdehyde,catalase activity and antioxidant capacity(FRAP)in saliva.The antioxidant profile of studied tea samples(FRAP,polyphenols,flavonoids)was positively correlated with salivary SFR,TPC,SH and FRAP but negatively correlated with salivary uric acid concentration in saliva.

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

Changes of the glutathione redox system during the weaning transition in piglets, in relation to small intestinal morphology and barrier function

Background: Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione(GSH)redox system. Therefore, these parameters were simultaneously measured throughout the weaning phase, in piglets differing in birth weight category and weaning age, as these pre-weaning factors are important determinants for the weaning transition. Low birth weight(LBW) and normal birth weight(NBW) littermates were assigned to one of three weaning treatments;i.e. weaning at 3 weeks of age(3 w), weaning at 4 weeks of age(4 w) and removal from the sow at 3 d of age and fed a milk replacer until weaning at 3 weeks of age(3 d3 w). For each of these treatments, six LBW and six NBW piglets were euthanized at 0, 2, 5, 12 or 28 d post-weaning piglets, adding up 180 piglets.Results: Weaning increased the glutathione peroxidase activity on d 5 post-weaning in plasma, and duodenal and jejunal mucosa. Small intestinal glutathione-S-transferase activity gradually increased until d 12 post-weaning, and this was combined with a progressive rise of mucosal GSH up till d 12 post-weaning. Oxidation of the GSH redox status(GSH/GSSG Eh) was only observed in the small intestinal mucosa of 3 d3 w weaned piglets at d 5 postweaning. These piglets also demonstrated increased fluorescein isothiocyanate dextran(FD4) and horseradish peroxidase fluxes in the duodenum and distal jejunum during the experiment, and specifically demonstrated increased FD4 fluxes at d 2 to d 5 post-weaning. On the other hand, profound villus atrophy was observed during the weaning transition for all weaning treatments. Finally, LBW and NBW piglets did not demonstrate notable differences in GSH redox status, small intestinal barrier function and histo-morphology throughout the experiment.Conclusion: Although moderate changes in the GSH redox system were observed upon weaning, the GSH redox status remained at a steady state level in 3 w and 4 w weaned piglets and was therefore not associated with weaning induced villus atrophy. Conversely, 3 d3 w weaned piglets demonstrated GSH redox imbalance in the small intestinal mucosa, and this co-occurred with a temporal malfunction of their intestinal barrier function.

Red onion extract(Allium cepa L.)supplementation improves redox balance in oxidatively stressed rats

Onions,consumed worldwide,are a good source of dietary phytochemicals with proven antioxidant properties.Catechin and quercetin are the most common and widely consumed flavonoids.The present study aimed to investigate the possible protective effect of onion extract as well as flavonoids(catechin and quercetin)on rats subjected to oxidative stress by mercuric chloride(HgCl2)treatment.Experiments were conducted on rat erythrocytes,which are a good model system to study oxidative stress.Results show that the oxidative stress induced by HgCl2 in Wistar rats resulted in substantially increased erythrocyte lipid peroxidation and higher activity of red cell plasma membrane redox system(PMRS)along with corresponding decrease in the intracellular reduced glutathione and antioxidant activity.Onion extract supplementation significantly(P<0.05)attenuated these adverse effects of HgCl2.Flavonoid supplementation resulted in a slightly higher antioxidant response compared to onion extract.We conclude that supplementation of these flavonoids results in normalization of erythrocyte PMRS activity which provides onion(rich in quercetin),a novel mechanism to exert its antioxidant effect against HgCl2-induced oxidative stress in rat erythrocytes in vivo.©2013 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Antioxidant and Immunopotentiating Effects of <i>Cordyceps </i>Mycelium Extract, Chicken Essence, and Their Combination in Experimental Models

Cordyceps mycelium extract (Cs-4), Chicken Essence (CE), and their combination were investigated for antioxidant and immunomodulatory activities in mouse models. Long-term treatment with Cs-4 or CE at equivalent human doses improved antioxidant status in various tissues, as evidenced by the enhancement of mitochondrial glutathione redox status in the brain, liver, heart, and kidney of mice. Cs-4 or CE treatment also produced an immunomodulatory action, as indicated by the potentiation of Concanavalin A-/lipopolysaccharide-induced proliferation of mouse splenocytes ex vivo. While doubling of the equivalent human doses of Cs-4 and CE did not further enhance their antioxidant or immunopotentiating effects, the combined treatment with Cs-4 and CE at their respective equivalent human doses produced an additive effect, with the extents of stimulation being larger than those produced by Cs-4 or CE alone. The results have demonstrated for the first time that the combined use of Cs-4 and CE can produce an additive effect on both antioxidation and immunopotentiation that cannot otherwise be achieved by increasing the equivalent human doses of Cs-4 or CE alone.

A Gene Expression Profiling of Early Rice Stamen Development that Reveals Inhibition of Photosynthetic Genes by OsMADS58

Stamen is a unique plant organ wherein germ cells or microsporocytes that commit to meiosis are initiated from somatic cells during its early developmental process. While genes determining stamen identity are known according to the ABC model of floral development, little information is available on how these genes affect germ cell initiation. By using the Affymetrix GeneChip Rice Genome Array to assess 51 279 tran- scripts, we established a dynamic gene expression profile （GEP） of the early developmental process of rice （Oryza sativa） stamen. Systematic analysis of the GEP data revealed novel expression patterns of some developmentally important genes including meiosis-, tapetum-, and phytohormone-related genes. Following the finding that a substantial amount of nuclear genes encoding photosynthetic proteins are ex- pressed at the low levels in early rice stamen, through the ChlP-seq analysis we found that a C-class MADS box protein, OsMADS58, binds many nuclear-encoded genes participated in photosystem and light reac- tions and the expression levels of most of them are increased when expression of OsMADS58 is downre- gulated in the osmads58 mutant. Furthermore, more pro-chloroplasts are observed and increased signals of reactive oxygen species are detected in the osmads58 mutant anthers. These findings implicate a novel link between stamen identity determination and hypoxia status establishment.

Reactive oxygen species in the progression and treatment of malignant mesothelioma

Malignant mesothelioma(MM)is an aggressive cancer that affects the pleural and peritoneal mesothelial lining of the lungs and abdomen.Survival rates for patients with MM remain extremely low and effective treatments are limited.MM tumors harbor both genotypic and phenotypic features that indicate MM tumor cells are under increased oxidative stress,similar to other aggressive cancers.This increased oxidative stress in MM cells supports aggressive growth while providing a therapeutic vulnerability exploitable by redox-modulating compounds.MM tumor cells also exhibit altered mitochondrial structure and function that contribute to the disease through perturbations in metabolism and reactive oxygen species(ROS)production and metabolism.Targeting the altered redox status in cancer through increasing cellular ROS levels directly or inhibiting cellular antioxidant pathways and disrupting ROS scavenging mechanisms has become an exciting area for therapeutic intervention.This review discusses ROS sources and signaling,mitochondrial structure and function and targeting mitochondria ROS as a therapeutic approach for the treatment of MM.