Oxidative stress and genetic markers of suboptimal antioxidant defense in the aging brain: a theoretical review.
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ABSTRACT:
SUBMITTER: Salminen LE
PROVIDER: S-EPMC6378111 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The aim of the present study was to establish whether markers of oxidative stress and the enzymatic defense system of the blood are related to moderate physical activity in younger old and the oldest old men. They were divided into four groups according to the age and level of physical activity (groups YN and YA-inactive and active younger old men aged 65-74 years, groups ON and OA-inactive and active oldest old men aged 90-99 years). Venous blood was collected from the subjects in the morning before breakfast. MDA concentration and antioxidant enzyme activities (SOD, CAT, GPx, and GR) in erythrocyte hemolysates were assayed. The concentration of isoprostanes (8-iso-PGF2α) and carbonyl groups in protein (CP) was measured in plasma and serum. All assayed antioxidant enzyme activities and the SOD/GPx ratios were significantly higher in the active younger old males than in all the inactive ones. In the group of oldest old active participants, only the GPx activity was significantly higher compared to the inactive oldest old males. The activity of CAT and GPx in the younger old inactive men was significantly lower than that in the oldest old inactive subjects. However, SOD, CAT, and GR activities and SOD/GPx ratio were significantly higher in the younger old active men compared to the oldest old active participants. The concentrations of isoprostanes, protein carbonyls, and MDA were significantly lower in both active and inactive younger old males than in the respective groups of the oldest old men and in both groups of active men, independently of age, compared to the respective inactive subjects. The present study confirmed that oxidative stress is related to age. Physical activity caused a decrease of oxidative stress markers independently of age and resulted in an increase of GPx activity in both younger old and the oldest old active groups.
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Project description:The biological mechanisms that give rise to age-related hearing loss (ARHL) are still poorly understood. However, there is growing recognition that oxidative stress may be an important factor. To address this issue, we measured the changes in the expression of cochlear oxidative stress and antioxidant defense-related genes in young (2 months old), middle-aged (12 months old), and old (21-25 months old) Fischer 344/NHsd (F344/NHsd) rats and compared gene expression changes with ARHL. A quantitative real-time reverse transcription polymerase chain reaction array revealed a significant age-related downregulation of only 1 gene, stearoyl-coenzyme A desaturase 1, and upregulation of 12 genes: 24-dehydrocholesterol reductase; aminoadipate-semialdehyde synthase; cytoglobin; dual oxidase 2; glutathione peroxidase 3; glutathione peroxidase 6; glutathione S-transferase, kappa 1; glutathione reductase; nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase, quinone 1; solute carrier Family 38, Member 5; thioredoxin interacting protein; and vimentin. Statistical analyses revealed significant correlations between gene expression and auditory function in 8 genes. Our results identified specific subsets of oxidative stress genes that appear to play an important role in ARHL in the Fischer 344/NHsd rat.
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Project description:BackgroundSnakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required.MethodsCases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database.ResultsPrincipal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity.ConclusionsOur results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.
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Project description:BACKGROUND: Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. METHODS: We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selected from 8 primary health care centers (PHCCs). We assessed classical CVD risk factors, plasma oxidized low-density lipoproteins (ox-LDL), and glutathione peroxidase (GSH-Px) using multilevel statistical procedures. RESULTS: Mean GSH-Px value was 612 U/L (SE: 12 U/L), with variation between PHCCs ranging from 549 to 674 U/L (Variance = 013.5; P<0.001). Between-participants variability within a PHCC accounted for 89% of the total variation. Both glucose and oxidized LDL were positively associated with GSH-Px activity after adjustment for possible confounder variables (P = 0.03 and P = 0.01, respectively). CONCLUSION: In a population at high cardiovascular risk, a positive linear association was observed between plasma GSH-Px activity and both glucose and ox-LDL levels. The high GSH-Px activity observed when an oxidative stress situation occurred, such as hyperglycemia and lipid oxidative damage, could be interpreted as a healthy defensive response against oxidative injury in our cardiovascular risk population.
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