Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Research on the synthesis of superoxide dismutase mimics by chemical and biologi-cal synthetic methods were reviewed.The advantages and limitations were analyzed.A prospect for the future development of superoxide dis...Research on the synthesis of superoxide dismutase mimics by chemical and biologi-cal synthetic methods were reviewed.The advantages and limitations were analyzed.A prospect for the future development of superoxide dismutase mimics is proposed.展开更多
Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Sin...Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.展开更多
Superoxide dismutases(SODs) were purified to homogeneity from Allium Sativum by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose(DE52) and Sephadex G-75. Based on sodium dodecyl su...Superoxide dismutases(SODs) were purified to homogeneity from Allium Sativum by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose(DE52) and Sephadex G-75. Based on sodium dodecyl sulfate\|polyacrylamide gel electrophoresis(SDS-AGE), Allium Sativum is predicted to contain four SODs. The molecular weights of the native SODs are 41 3 kD, 37 0 kD, 35 2 kD and 31 0 kD, which consist of subunits of 20 7 kD, 18 4 kD, 17 7 kD and 15 4 kD respectively. Because of their specific sensitivity to hydrogen peroxide, cyanogens potassium and chloroform\|alcohol, the SODs in Allium Sativum appear to be Cu, Zn-SOD isoenzymes. The isoelectric analysis indicates that three of the four isoenzymes are acidic proteins with isoelectric points at pH 3 5, 3 7 and 4 0, respectively, and the fourth one is a basic protein with isoeletric point at pH 8 5.展开更多
Mammalian cells express two isoforms of Cu- and Zn-containing superoxide dismutases（SODs）, CuZn-SOD and extracellular SOD（EC-SOD）, involved in the defense system against reactive oxygen species（ROS）. The two SOD...Mammalian cells express two isoforms of Cu- and Zn-containing superoxide dismutases（SODs）, CuZn-SOD and extracellular SOD（EC-SOD）, involved in the defense system against reactive oxygen species（ROS）. The two SODs have structurally homologous centre domain with distinct N- and C-terminuses, resulting in the different characteristics of the structure and function of the two molecules. We generated a hybrid SOD molecule（namely hy- SOD） via replacing the N- and C-terminuses of hCuZnSOD with the counterparts of hEC-SOD. The hySOD was expressed in host Pichia pastoris and the purified protein was a dimer with a molecular weight of about 34000. A series of activity analyses indicates that the hySOD is similar to hEC-SOD in heat-stability, and has the activity of protecting the host cell against heat shock and oxidative stress. Our results show evidence for the study on the compound activity of multiple SOD molecules, and may be important for understanding the relationship between structure and function of hEC-SOD and hCuZnSOD.展开更多
Increase uric acid levels have been found in oxidative stress. Urate radicals do not react with oxygen to form another peroxy radical, thus increasing the efficacy of uric acid as an antioxidant. Therefore, this study...Increase uric acid levels have been found in oxidative stress. Urate radicals do not react with oxygen to form another peroxy radical, thus increasing the efficacy of uric acid as an antioxidant. Therefore, this study is designed to measure the level of uric acids and find out the relationship of uric acid with superoxide dismutase in induced hyperuricemic model. Forty male albino rats with an average weight of 180 ± 2 g were selected. The rats were grouped. The animals were fed on standard diet and given tap water ad libitum until treatment. Albino rats were divided into four groups. Group A(10)-control given only standard diet, group B(10) fed on 60% fructose with standard diet , group C(10) fed on fructose, standard diet and intraperitonially oxonic acid 250 mg/kg and group D (10) only on injection intraperotonially oxonic acid 250 mg/kg. At the end of study 10 mL of blood was drawn from heart of rats. Then blood was estimated for superoxide dismutase and uric acids done by kit methods randox-manual/Rx monza UA230/UA 233. Results: In Group C superoxide dismutase was found to be 32 % (244 mg/dL ± 2.23) more than control. In the same group the uric acid concentration was highly significantly correlated with control. Conclusion: The uric acid concentration increases when we take fructose up to 60% in our diet. It also increases superoxide dismutase concentration. More than this value may have inverse effect on the uric acid level and its role as an antioxidant may become inversed.展开更多
A superoxide dismutase（ SOD ） was purified to homogeneity from fresh camellia pollen by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose（ DE52 ）, Sephadex G-100 and phenyl seph...A superoxide dismutase（ SOD ） was purified to homogeneity from fresh camellia pollen by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose（ DE52 ）, Sephadex G-100 and phenyl sepharose^TM 6 Fast Flow columns. Its specific activity could reach to 4034 U/mg protein and it was determined to be Cu/ Zn-SOD according to its different sensitivities to different inhibitors. The molecular weight of the SOD and its subunit were 69500 and 34700, respectively, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis （SDS- PAGE）, which implicates that the SOD in camellia pollen is a dimmer composed of two identical subunits. The isoelectric point of the enzyme was determined to be 4. 1 by isoelectric focusing electrophoresis and the N-terminal amino acid was identified to be Gly by the DNS-Cl method. Its α-Helix was also calculated to be approximately 21.8% according to the circular dichroism（CD） spectra.展开更多
Plants produce reactive oxygen species(ROS) to defend pathogens. To counteract this attack, certain pathogens express superoxide dismutases(SODs) to scavenge host-derived ROS. However, the roles of SODs in Verticilliu...Plants produce reactive oxygen species(ROS) to defend pathogens. To counteract this attack, certain pathogens express superoxide dismutases(SODs) to scavenge host-derived ROS. However, the roles of SODs in Verticillium dahliae, an important vascular pathogen, are not clear. Our previous study has shown that a putative extracellular SOD(VdSOD5) of V. dahliae is significantly induced by culturing in cotton tissues, suggesting that VdSOD5 may play an important role in host–pathogen interactions and virulence. Here, we showed that VdSOD5 encoded a superoxide dismutase with a cofactor copper-binding site and a functional signal peptide that can conduct protein secretion in an invertase-mutated yeast strain. The mutations in VdSOD5(ΔVdSOD5) did not change the normal vegetative growth and conidial production but reduced the virulence of V. dahliae on susceptible host cotton. Further studies showed that the transcription of Vd SOD5 was significantly up-regulated during the early stage of infection, and the loss-of-function of VdSOD5 decreased culture filtrate and fungal tissue SOD activities of V. dahliae by 74 and 28%, respectively. Compared to the wild-type strain Vd991, the ΔVdSOD5 showed the same sensitivity to the intracellular ROS generator menadione. Furthermore, nitroblue tetrazolium(NBT) staining demonstrated that VdSOD5 functioned in the detoxification of superoxides generated by host roots during infection. These results suggest that VdSOD5 of V. dahliae is an important virulence factor, secreted out of cells to combat host-derived ROS.展开更多
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
文摘Research on the synthesis of superoxide dismutase mimics by chemical and biologi-cal synthetic methods were reviewed.The advantages and limitations were analyzed.A prospect for the future development of superoxide dismutase mimics is proposed.
文摘Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases,the discovery of this gene has been crucial for amyotrophic lateral sclerosis research.Since the identification of superoxide dismutase 1 in 1993,the field of amyotrophic lateral sclerosis genetics has considerably widened,improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis.In this review,we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients.Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients,but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations.We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation.Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis,enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes,which is important for the therapeutic strategy targeting genetic mutations.Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors,including environment and other unidentified agents including modifier genes.
基金Supported by the Chinese Universities Education Science"Ten- five" Program ( 2 0 0 2 ,2 0 - 5 8- 4 7)
文摘Superoxide dismutases(SODs) were purified to homogeneity from Allium Sativum by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose(DE52) and Sephadex G-75. Based on sodium dodecyl sulfate\|polyacrylamide gel electrophoresis(SDS-AGE), Allium Sativum is predicted to contain four SODs. The molecular weights of the native SODs are 41 3 kD, 37 0 kD, 35 2 kD and 31 0 kD, which consist of subunits of 20 7 kD, 18 4 kD, 17 7 kD and 15 4 kD respectively. Because of their specific sensitivity to hydrogen peroxide, cyanogens potassium and chloroform\|alcohol, the SODs in Allium Sativum appear to be Cu, Zn-SOD isoenzymes. The isoelectric analysis indicates that three of the four isoenzymes are acidic proteins with isoelectric points at pH 3 5, 3 7 and 4 0, respectively, and the fourth one is a basic protein with isoeletric point at pH 8 5.
文摘Mammalian cells express two isoforms of Cu- and Zn-containing superoxide dismutases（SODs）, CuZn-SOD and extracellular SOD（EC-SOD）, involved in the defense system against reactive oxygen species（ROS）. The two SODs have structurally homologous centre domain with distinct N- and C-terminuses, resulting in the different characteristics of the structure and function of the two molecules. We generated a hybrid SOD molecule（namely hy- SOD） via replacing the N- and C-terminuses of hCuZnSOD with the counterparts of hEC-SOD. The hySOD was expressed in host Pichia pastoris and the purified protein was a dimer with a molecular weight of about 34000. A series of activity analyses indicates that the hySOD is similar to hEC-SOD in heat-stability, and has the activity of protecting the host cell against heat shock and oxidative stress. Our results show evidence for the study on the compound activity of multiple SOD molecules, and may be important for understanding the relationship between structure and function of hEC-SOD and hCuZnSOD.
文摘Increase uric acid levels have been found in oxidative stress. Urate radicals do not react with oxygen to form another peroxy radical, thus increasing the efficacy of uric acid as an antioxidant. Therefore, this study is designed to measure the level of uric acids and find out the relationship of uric acid with superoxide dismutase in induced hyperuricemic model. Forty male albino rats with an average weight of 180 ± 2 g were selected. The rats were grouped. The animals were fed on standard diet and given tap water ad libitum until treatment. Albino rats were divided into four groups. Group A(10)-control given only standard diet, group B(10) fed on 60% fructose with standard diet , group C(10) fed on fructose, standard diet and intraperitonially oxonic acid 250 mg/kg and group D (10) only on injection intraperotonially oxonic acid 250 mg/kg. At the end of study 10 mL of blood was drawn from heart of rats. Then blood was estimated for superoxide dismutase and uric acids done by kit methods randox-manual/Rx monza UA230/UA 233. Results: In Group C superoxide dismutase was found to be 32 % (244 mg/dL ± 2.23) more than control. In the same group the uric acid concentration was highly significantly correlated with control. Conclusion: The uric acid concentration increases when we take fructose up to 60% in our diet. It also increases superoxide dismutase concentration. More than this value may have inverse effect on the uric acid level and its role as an antioxidant may become inversed.
文摘A superoxide dismutase（ SOD ） was purified to homogeneity from fresh camellia pollen by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose（ DE52 ）, Sephadex G-100 and phenyl sepharose^TM 6 Fast Flow columns. Its specific activity could reach to 4034 U/mg protein and it was determined to be Cu/ Zn-SOD according to its different sensitivities to different inhibitors. The molecular weight of the SOD and its subunit were 69500 and 34700, respectively, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis （SDS- PAGE）, which implicates that the SOD in camellia pollen is a dimmer composed of two identical subunits. The isoelectric point of the enzyme was determined to be 4. 1 by isoelectric focusing electrophoresis and the N-terminal amino acid was identified to be Gly by the DNS-Cl method. Its α-Helix was also calculated to be approximately 21.8% according to the circular dichroism（CD） spectra.
基金supported by the National Natural Science Foundation of China (31501588, 31972228, and 31970142)。
文摘Plants produce reactive oxygen species(ROS) to defend pathogens. To counteract this attack, certain pathogens express superoxide dismutases(SODs) to scavenge host-derived ROS. However, the roles of SODs in Verticillium dahliae, an important vascular pathogen, are not clear. Our previous study has shown that a putative extracellular SOD(VdSOD5) of V. dahliae is significantly induced by culturing in cotton tissues, suggesting that VdSOD5 may play an important role in host–pathogen interactions and virulence. Here, we showed that VdSOD5 encoded a superoxide dismutase with a cofactor copper-binding site and a functional signal peptide that can conduct protein secretion in an invertase-mutated yeast strain. The mutations in VdSOD5(ΔVdSOD5) did not change the normal vegetative growth and conidial production but reduced the virulence of V. dahliae on susceptible host cotton. Further studies showed that the transcription of Vd SOD5 was significantly up-regulated during the early stage of infection, and the loss-of-function of VdSOD5 decreased culture filtrate and fungal tissue SOD activities of V. dahliae by 74 and 28%, respectively. Compared to the wild-type strain Vd991, the ΔVdSOD5 showed the same sensitivity to the intracellular ROS generator menadione. Furthermore, nitroblue tetrazolium(NBT) staining demonstrated that VdSOD5 functioned in the detoxification of superoxides generated by host roots during infection. These results suggest that VdSOD5 of V. dahliae is an important virulence factor, secreted out of cells to combat host-derived ROS.
