Effect of Fe nutrition on Fe acquisition, aconitase enzyme activity and assimilation of the element in ferritin protein was studied in two indica rice cultivars viz. Sharbati and Lalat having contrasting grain Fe conc...Effect of Fe nutrition on Fe acquisition, aconitase enzyme activity and assimilation of the element in ferritin protein was studied in two indica rice cultivars viz. Sharbati and Lalat having contrasting grain Fe concentration. Young rice seedlings were grown in hydroponics with different levels of Fe. For comparison, the two cultivars were also grown in the field under natural conditions of rice culture. Iron accumulation, aconitase activity and ferritin level were higher in the high Fe containing cultivar, Sharbati than that in the low Fe containing cultivar, Lalat. While aconitase activity increased consistently with the increase in concentration of Fe in the growing medium, the same was not found to be true for accumulation of ferritin protein. The leaf ferritin level increased up to a certain level of Fe in the growing medium and declined thereafter. Levels of Fe in the growing medium giving maximum ferritin synthesis were found to be different in the two rice cultivars. In both cultivars, aconitase activity attained maximum level after 20 days of panicle emergence (heading). Pattern of Fe accumulation in the leaves in response to increasing Fe level in the nutrient solution paralleled with that of the aconitase activity indicating a positive correlation. It was concluded that accumulation of both ferritin protein and aconitase enzyme were influenced not only by the Fe level in the growing medium but also by the internal Fe concentration of the two cultivars.展开更多
The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding pla...The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding plays a role in ALS pathogenesis in two ways: non-ATG translation of the repeat can lead to aggregates of the known C9orf72 specific dipeptide polymer, whereas the repeat also can form neurotoxic RNA inclusions that dose-responsively kill motor neurons. We report the presence of a homology in the 5’untranslated region (UTR) of the messenger RNA encoding C9orf72 with the iron responsive elements (IRE) that control expression of iron-associated transcripts and predict that this RNA structure may iron-dependently regulate C9orf72 translation. We previously report altered serum ferritin levels track with severity of ALS in patients. Here, we conduct bioinformatics analyses to determine the secondary structure of the 5’UTR in C9orf72 mRNA and find it aligned with IREs in the human mitochondrial cis-aconitase and L and H-ferritin transcripts. Comparison of the role of RNA repeats in Friedriech’s ataxia and fragile X mental retardation suggests the utility of RNA based therapies for treatment of ALS. Antisense oligonucleotides (ASO) have been reported to therapeutically target these GGGGCC repeats. At the same time, because the function of C9orf72 is unknown, knockdown strategies carry some risk of inducing or compounding haploinsufficiency. We propose, for consideration, an approach that may enhance its therapeutic dynamic range by increasing the 5’UTR driven translation of C9orf72 protein to compensate for any potential ALS-specific or ASO-induced haploinsufficieny.展开更多
AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Ky...AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet （〈 6.5 mg Fe and 4.0 mg Zn/kg diet） for 4 wk were randomly divided into three groups （n = 8, each） and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron ＋ 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of SSFe or ^65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates （mitochondrial and cytosolic fractions）, were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS： Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION： Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.展开更多
On the model of Cu-induced liver fibrosis, the relationship between the activity of prooxidant-antioxidant system, immune system parameters, liver morphology and several physiological parameters (body temperature and ...On the model of Cu-induced liver fibrosis, the relationship between the activity of prooxidant-antioxidant system, immune system parameters, liver morphology and several physiological parameters (body temperature and performance ability of the animals, taking into account their ages) was investigated. Classical biochemical, immunological, histological and physiological methods of investigation were used. The subjects of the study were male Wistar rats of 3-month (young) and 20-month (old) age. For the induction of liver fibrosis, experimental animals were successively injected with copper sulfate (three times at intervals of 24 hours at a dose corresponding to 33% of the lethal one). It was shown that after five days of sulfate copper administration inflammatory reactions in the liver, damage of the vessel epithelium, an increase in collagen content, and other morphological changes were detected. At this time, the content of lipid hydroperoxides in the liver and blood serum was increased, the activity of a number of antioxidant enzymes was reduced, and the activity of aconitase was two times less compared to values in the control group. These changes correlated with a decrease in the amount and activity of phagocytic cells in the blood of experimental animals. Inhibition of the general metabolism was accompanied by a decrease in body temperature, loss of body weight and performance ability. The relationship between a specific metabolic pattern in animals with Cu-induced fibrosis was age-dependent. The formed specific adaptive metabolic pattern is unstable, and in the future it can be realized in one of three possible adaptive strategies, the choice of which is influenced by age.展开更多
In nature,organisms face multiple abiotic stress concurrently.Our previous study has indicated how threshold level of lethality depends on the type and combination of stressors.Many mechanisms exist by which organisms...In nature,organisms face multiple abiotic stress concurrently.Our previous study has indicated how threshold level of lethality depends on the type and combination of stressors.Many mechanisms exist by which organisms respond to stressors and maintain homeostasis.We examined the homeostatic pliability in an extremophilic oriental midge Chironomus ramosus larvae under various combinatorial stress conditions of desiccation(DS),heat(HS)and starvation(SS).Exposure to these stressors led to activation of a common response pathway of oxidative stress.Abundance of antioxidant enzymes like superoxide dismutase,catalase,glutathione reductase and glutathione peroxidase along with selective as well as stressor specific increase in total antioxidant capacity were reflected from the corresponding level of reactive oxygen and nitrogen species(RONS)in larvae exposed to various combinatorial stress.Additionally,we found stressor specific increment in lipid peroxidation level,protein carbonyl content and advanced oxidative protein products during the stress regime.Further investigation revealed a sharp decline in the activity of mitochondrial aconitase enzyme activity in response to abiotic stress induced oxidative stress.The combinatorial stressor specific comparative study based on biochemical and fluorescence based redox-endpoint assays confirmed that the generation of oxidative stress is the consequential convergent pathway of DS,HS and SS,but the quantum of RONS decides the redox potential of homeostatic response and survival rate.展开更多
文摘Effect of Fe nutrition on Fe acquisition, aconitase enzyme activity and assimilation of the element in ferritin protein was studied in two indica rice cultivars viz. Sharbati and Lalat having contrasting grain Fe concentration. Young rice seedlings were grown in hydroponics with different levels of Fe. For comparison, the two cultivars were also grown in the field under natural conditions of rice culture. Iron accumulation, aconitase activity and ferritin level were higher in the high Fe containing cultivar, Sharbati than that in the low Fe containing cultivar, Lalat. While aconitase activity increased consistently with the increase in concentration of Fe in the growing medium, the same was not found to be true for accumulation of ferritin protein. The leaf ferritin level increased up to a certain level of Fe in the growing medium and declined thereafter. Levels of Fe in the growing medium giving maximum ferritin synthesis were found to be different in the two rice cultivars. In both cultivars, aconitase activity attained maximum level after 20 days of panicle emergence (heading). Pattern of Fe accumulation in the leaves in response to increasing Fe level in the nutrient solution paralleled with that of the aconitase activity indicating a positive correlation. It was concluded that accumulation of both ferritin protein and aconitase enzyme were influenced not only by the Fe level in the growing medium but also by the internal Fe concentration of the two cultivars.
文摘The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding plays a role in ALS pathogenesis in two ways: non-ATG translation of the repeat can lead to aggregates of the known C9orf72 specific dipeptide polymer, whereas the repeat also can form neurotoxic RNA inclusions that dose-responsively kill motor neurons. We report the presence of a homology in the 5’untranslated region (UTR) of the messenger RNA encoding C9orf72 with the iron responsive elements (IRE) that control expression of iron-associated transcripts and predict that this RNA structure may iron-dependently regulate C9orf72 translation. We previously report altered serum ferritin levels track with severity of ALS in patients. Here, we conduct bioinformatics analyses to determine the secondary structure of the 5’UTR in C9orf72 mRNA and find it aligned with IREs in the human mitochondrial cis-aconitase and L and H-ferritin transcripts. Comparison of the role of RNA repeats in Friedriech’s ataxia and fragile X mental retardation suggests the utility of RNA based therapies for treatment of ALS. Antisense oligonucleotides (ASO) have been reported to therapeutically target these GGGGCC repeats. At the same time, because the function of C9orf72 is unknown, knockdown strategies carry some risk of inducing or compounding haploinsufficiency. We propose, for consideration, an approach that may enhance its therapeutic dynamic range by increasing the 5’UTR driven translation of C9orf72 protein to compensate for any potential ALS-specific or ASO-induced haploinsufficieny.
文摘AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet （〈 6.5 mg Fe and 4.0 mg Zn/kg diet） for 4 wk were randomly divided into three groups （n = 8, each） and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron ＋ 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of SSFe or ^65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates （mitochondrial and cytosolic fractions）, were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS： Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION： Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.
文摘On the model of Cu-induced liver fibrosis, the relationship between the activity of prooxidant-antioxidant system, immune system parameters, liver morphology and several physiological parameters (body temperature and performance ability of the animals, taking into account their ages) was investigated. Classical biochemical, immunological, histological and physiological methods of investigation were used. The subjects of the study were male Wistar rats of 3-month (young) and 20-month (old) age. For the induction of liver fibrosis, experimental animals were successively injected with copper sulfate (three times at intervals of 24 hours at a dose corresponding to 33% of the lethal one). It was shown that after five days of sulfate copper administration inflammatory reactions in the liver, damage of the vessel epithelium, an increase in collagen content, and other morphological changes were detected. At this time, the content of lipid hydroperoxides in the liver and blood serum was increased, the activity of a number of antioxidant enzymes was reduced, and the activity of aconitase was two times less compared to values in the control group. These changes correlated with a decrease in the amount and activity of phagocytic cells in the blood of experimental animals. Inhibition of the general metabolism was accompanied by a decrease in body temperature, loss of body weight and performance ability. The relationship between a specific metabolic pattern in animals with Cu-induced fibrosis was age-dependent. The formed specific adaptive metabolic pattern is unstable, and in the future it can be realized in one of three possible adaptive strategies, the choice of which is influenced by age.
基金supported by University Grant Commission’s Centre for Advanced Studies research grant allocated fund(Grant No.287 Zoology Phase-III)supports were obtained from the Indo-Israel Research Grant(4th cycle).
文摘In nature,organisms face multiple abiotic stress concurrently.Our previous study has indicated how threshold level of lethality depends on the type and combination of stressors.Many mechanisms exist by which organisms respond to stressors and maintain homeostasis.We examined the homeostatic pliability in an extremophilic oriental midge Chironomus ramosus larvae under various combinatorial stress conditions of desiccation(DS),heat(HS)and starvation(SS).Exposure to these stressors led to activation of a common response pathway of oxidative stress.Abundance of antioxidant enzymes like superoxide dismutase,catalase,glutathione reductase and glutathione peroxidase along with selective as well as stressor specific increase in total antioxidant capacity were reflected from the corresponding level of reactive oxygen and nitrogen species(RONS)in larvae exposed to various combinatorial stress.Additionally,we found stressor specific increment in lipid peroxidation level,protein carbonyl content and advanced oxidative protein products during the stress regime.Further investigation revealed a sharp decline in the activity of mitochondrial aconitase enzyme activity in response to abiotic stress induced oxidative stress.The combinatorial stressor specific comparative study based on biochemical and fluorescence based redox-endpoint assays confirmed that the generation of oxidative stress is the consequential convergent pathway of DS,HS and SS,but the quantum of RONS decides the redox potential of homeostatic response and survival rate.
