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A New Nano Antioxidant Prevention and Therapy Delivery System
Tg female mice at 1.5–2 years of age also showed a significant improvement in neuromuscular fitness (evaluated by the Rotarod test) and in the maximum and mean grip strength, both parameters related to frailty. Our data point out that G6PD overexpression in mice protects against ROS-derived damage at old age.
doi: 10.1016/j.freeradbiomed.2016.10.224 184 Redox-Markers in the European MARK-AGE Study Daniela Weber1, Wolfgang Stuetz2, and Tilman Grune1 1 German Institute of Human Nutrition, Nuthetal, Germany, 2 University of Hohenheim, Stuttgart, Germany Redox markers have been associated with age and disease status in various human studies. It is known that life expectancy is increasing, whereas health span, i.e. the disease-free period in a person’s life, remains constant. This means that although humans reach higher age, the disease-ridden period may prevail. Biomarkers reflecting ageing and health span are of increasing interest to monitor and possibly even intervene in these processes. However, so far redox markers have never been assessed in a large number of samples in the general healthy population in relation to age. We here present results on oxidative stress markers of the European MARK-AGE study, an observational cross-sectional study in seven countries with 3,000 participants aiming to identify a set of biomarkers of ageing. The study comprised three different groups: 1) subjects aged 3574 recruited in an age-stratified manner from the healthy general population (HG; n = 2,200), 2) offspring from centenarians (CO; n = 500) as well as 3) spouses of centenarian-offspring (SCO; n = 300). Our results indicate that the three groups differ significantly in biomarkers of protein oxidation, lipid peroxidation, glycation and also the activity of protein degradation systems and repair enzymes. Interestingly, none of the analyzed parameters differed significantly between CO and SCO. In contrast, most parameters were statistically significantly different between HG and CO as well as between HG and SCO. Since CO and SCO did not differ in any of the assessed biomarkers, lifestyle is one likely contributor for the altered redox status, offering a promising approach for intervention studies. However, before intervention studies are carried out, the reason for the altered redox markers in these groups should be further investigated as they might also be influenced by metabolism and genetics.
doi: 10.1016/j.freeradbiomed.2016.10.225 185 A New Nano Antioxidant Prevention and Therapy Delivery System Yang-Liu1, Libo Du1, and Yuming Zhao2 1 Institute of Chemistry, Chinese Academy of Science, Beijing, People's Republic of China, 2Capital Medical University, Beijing, People's Republic of China
neurodegenerative diseases and stroke. However, the clinical application of antioxidants is limited probably due to their poor bioavailability and low biocompatibility. Here we introduce a novel strategy for fabrication of antioxidant-loaded ultra-small nanovehicles (particle sizes range from 30 to 50 nm). The nano-vehicles exhibited more excellent cellular uptake and intensive accumulation in central nervous system in vivo in comparison with the antioxidant monomers. Furthermore, we examined their bioactivities against reactive oxygen species (ROS)-related oxidative damage in neurodegenerative conditions. Compared with their monomer, the nano-encapsulated antioxidants showed more intensive effects on inhibiting hypoxiamediated neuronal loss, ROS-induced amyloid β releasing and apoptosis of nerve cells as well as macrophages damage. In addition, the nanoencapsulated antioxidants also exerted significant neuroprotection in the middle cerebral artery occlusion mimicked stroke insults. The results further indicate that the nanovehicles can high-efficiently act against mitochondria-involved apoptosis. Consequently, the new nano-vehicles possibly provide an ideal platform for its application in the intervention and therapy of various ROS-related neurological diseases.
doi: 10.1016/j.freeradbiomed.2016.10.226 186 Aging of Antioxidant Inducibility in Human Lung Epithelial Cells Partially Mimics Aging in Animal Studies Lulu Zhou1 1 University of Southern California, Los Angeles, USA The antioxidant/inflammatory steady state shifts downward in aging. Based on previous reports of a decreased ability to activate the Nrf2 pathway in animal studies, we hypothesized that the ability to activate Nrf2 would decline in primary human cells with age, but that the basal expression of NF-B-regulated genes would be greater with age. Six batches of Primary human bronchial epithelial (HBE) cells were obtained from 6 different subjects of age 29, 28, 67 and 69 (male, non-smoker) and were randomly paired into 3 groups. Cells of low passage were treated with or without 2 μM sulforaphane for 12 hours, and the mRNAs of Nrf2-regulated antioxidant (phase II) genes were measured. Unstimulated expression of GCLC, GCLM, HO1 and NQO1 genes were the same in the young and old HBE. In contrast, sulforaphane-induced phase II gene expression of the older HBE cells decreased compared with that in the younger cells supporting our hypothesis. Young cells also produced an increased expression in luciferasegreen fluorescent protein after EpRE-luciferase transfection followed by 12 hours’ stimulation with sulforaphane compared to the cells from the elderly, which indicates enhanced Nrf2 activation. This result further suggests stronger detoxification response in younger HBE cells to electrophiles. Western blot analysis showed an increase in Nrf2 accumulation within 1 hour in cell nucleus after stimulation with sulforaphane in both young and old cells. Bach-1 and c-myc which are Nrf2 suppressors were subsequently quantified at baseline and after stimulation. This mimics what has been observed in several previously reported studies of animal organs. Supported by NIH grant ES023864.
doi: 10.1016/j.freeradbiomed.2016.10.227
Oxidative stress has been proven to be a vital pathogenesis of
S90
SfRBM / SFRRI 2016
doi: 10.1016/j.freeradbiomed.2016.10.224 184 Redox-Markers in the European MARK-AGE Study Daniela Weber1, Wolfgang Stuetz2, and Tilman Grune1 1 German Institute of Human Nutrition, Nuthetal, Germany, 2 University of Hohenheim, Stuttgart, Germany Redox markers have been associated with age and disease status in various human studies. It is known that life expectancy is increasing, whereas health span, i.e. the disease-free period in a person’s life, remains constant. This means that although humans reach higher age, the disease-ridden period may prevail. Biomarkers reflecting ageing and health span are of increasing interest to monitor and possibly even intervene in these processes. However, so far redox markers have never been assessed in a large number of samples in the general healthy population in relation to age. We here present results on oxidative stress markers of the European MARK-AGE study, an observational cross-sectional study in seven countries with 3,000 participants aiming to identify a set of biomarkers of ageing. The study comprised three different groups: 1) subjects aged 3574 recruited in an age-stratified manner from the healthy general population (HG; n = 2,200), 2) offspring from centenarians (CO; n = 500) as well as 3) spouses of centenarian-offspring (SCO; n = 300). Our results indicate that the three groups differ significantly in biomarkers of protein oxidation, lipid peroxidation, glycation and also the activity of protein degradation systems and repair enzymes. Interestingly, none of the analyzed parameters differed significantly between CO and SCO. In contrast, most parameters were statistically significantly different between HG and CO as well as between HG and SCO. Since CO and SCO did not differ in any of the assessed biomarkers, lifestyle is one likely contributor for the altered redox status, offering a promising approach for intervention studies. However, before intervention studies are carried out, the reason for the altered redox markers in these groups should be further investigated as they might also be influenced by metabolism and genetics.
doi: 10.1016/j.freeradbiomed.2016.10.225 185 A New Nano Antioxidant Prevention and Therapy Delivery System Yang-Liu1, Libo Du1, and Yuming Zhao2 1 Institute of Chemistry, Chinese Academy of Science, Beijing, People's Republic of China, 2Capital Medical University, Beijing, People's Republic of China
neurodegenerative diseases and stroke. However, the clinical application of antioxidants is limited probably due to their poor bioavailability and low biocompatibility. Here we introduce a novel strategy for fabrication of antioxidant-loaded ultra-small nanovehicles (particle sizes range from 30 to 50 nm). The nano-vehicles exhibited more excellent cellular uptake and intensive accumulation in central nervous system in vivo in comparison with the antioxidant monomers. Furthermore, we examined their bioactivities against reactive oxygen species (ROS)-related oxidative damage in neurodegenerative conditions. Compared with their monomer, the nano-encapsulated antioxidants showed more intensive effects on inhibiting hypoxiamediated neuronal loss, ROS-induced amyloid β releasing and apoptosis of nerve cells as well as macrophages damage. In addition, the nanoencapsulated antioxidants also exerted significant neuroprotection in the middle cerebral artery occlusion mimicked stroke insults. The results further indicate that the nanovehicles can high-efficiently act against mitochondria-involved apoptosis. Consequently, the new nano-vehicles possibly provide an ideal platform for its application in the intervention and therapy of various ROS-related neurological diseases.
doi: 10.1016/j.freeradbiomed.2016.10.226 186 Aging of Antioxidant Inducibility in Human Lung Epithelial Cells Partially Mimics Aging in Animal Studies Lulu Zhou1 1 University of Southern California, Los Angeles, USA The antioxidant/inflammatory steady state shifts downward in aging. Based on previous reports of a decreased ability to activate the Nrf2 pathway in animal studies, we hypothesized that the ability to activate Nrf2 would decline in primary human cells with age, but that the basal expression of NF-B-regulated genes would be greater with age. Six batches of Primary human bronchial epithelial (HBE) cells were obtained from 6 different subjects of age 29, 28, 67 and 69 (male, non-smoker) and were randomly paired into 3 groups. Cells of low passage were treated with or without 2 μM sulforaphane for 12 hours, and the mRNAs of Nrf2-regulated antioxidant (phase II) genes were measured. Unstimulated expression of GCLC, GCLM, HO1 and NQO1 genes were the same in the young and old HBE. In contrast, sulforaphane-induced phase II gene expression of the older HBE cells decreased compared with that in the younger cells supporting our hypothesis. Young cells also produced an increased expression in luciferasegreen fluorescent protein after EpRE-luciferase transfection followed by 12 hours’ stimulation with sulforaphane compared to the cells from the elderly, which indicates enhanced Nrf2 activation. This result further suggests stronger detoxification response in younger HBE cells to electrophiles. Western blot analysis showed an increase in Nrf2 accumulation within 1 hour in cell nucleus after stimulation with sulforaphane in both young and old cells. Bach-1 and c-myc which are Nrf2 suppressors were subsequently quantified at baseline and after stimulation. This mimics what has been observed in several previously reported studies of animal organs. Supported by NIH grant ES023864.
doi: 10.1016/j.freeradbiomed.2016.10.227
Oxidative stress has been proven to be a vital pathogenesis of
S90
SfRBM / SFRRI 2016