GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI ...GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI contributes to at least fifty percent of GPX activity in rodent small intestmal epithelium. The total GPX activity consists of at least 70% of selenium-dependent GPX activity in this compartment.By analyzing a panel of mouse mterspecies DNA from the Jackson Laboratory's backcross resource,we mapped Gpx2 gene to mouse chromosome 12 between D12Mit4 and D12Mit5, near the Ccs1 locus which contains a colon cancer susceptibility gene. A pseudogene, Gpx2-ps is mapped to mouse chromosome 7.Comparison of Gpx2 gene expression in three pairs of C57BL/6Ha and ICR/Ha mice which are respectively resistant and sensitive to dimethylhydrazine-induced colon cancer, we found a higher Gpx2 mRNA level in C57BL/6Ha colon than ICR/Ha colon. Interestingly, a lower level of GPX activity is found in the resistant strain of mice. Because GPX-1 has three times higher specific activity than GPX GI, our data suggest that the decreased GPX activity may result from a higher level of Gpx2 gene expression in those cells co-express GPx1 gene展开更多
In the blood fluke Schistosoma mansoni a functionally active, monomeric, phospholipid hydroperoxide glutathione peroxidase (PHGPx) has been purified and characterized. This enzyme contains a catalytically active selen...In the blood fluke Schistosoma mansoni a functionally active, monomeric, phospholipid hydroperoxide glutathione peroxidase (PHGPx) has been purified and characterized. This enzyme contains a catalytically active selenocysteine. The protein has been shown to be the product of a cloned gene, previously referred to as a glutathione peroxidase gene. S. mansoni PHGPx has been found 5 times more abundant in female than in male worm extract. As in vertebrate PHGPx, homology alignment indicates that the residues involved in the glutathione binding by the tetrameric cellular glutathione peroxidase are mutated in the S. mansoni enzyme. Thus, this aspect appears a landmark of the PHGPx-type of glutathione peroxidases,which might be of functional relevance展开更多
We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord trans...We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was signiifcantly enhanced in the model group. Af-ter 8 weeks, the number of horseradish peroxidase-labeled nerve ifbers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and signiifcantly higher than in the model group. The newly formed nerve ifbers and myelinated ner ve ifbers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group.展开更多
The molecular basis for adaptations to extreme environments can now be understood by interrogating the everincreasing number of sequenced genomes.Mammals such as cetaceans,bats,and highland species can protect themsel...The molecular basis for adaptations to extreme environments can now be understood by interrogating the everincreasing number of sequenced genomes.Mammals such as cetaceans,bats,and highland species can protect themselves from oxidative stress,a disruption in the balance of reactive oxygen species,which results in oxidative injury and cell damage.Here,we consider the evolution of the glutathione peroxidase(GPX)family of antioxidant enzymes by interrogating publicly available genome data from 70 mammalian species from all major clades.We identified 8 GPX subclasses ubiquitous to all mammalian groups.Mammalian GPX gene families resolved into the GPX4/7/8 and GPX1/2/3/5/6 groups and are characterized by several instances of gene duplication and loss,indicating a dynamic process of gene birth and death in mammals.Seven of the eight GPX subfamilies(all but GPX7)were under positive selection,with the residues under selection located at or close to active sites or at the dimer interface.We also reveal evidence of a correlation between ecological niches(e.g.high oxidative stress)and the divergent selection and gene copy number of GPX subclasses.Notably,a convergent expansion of GPX1 was observed in several independent lineages of mammals under oxidative stress and may be important for avoiding oxidative damage.Collectively,this study suggests that the GPX gene family has shaped the adaption of mammals to stressful environments.展开更多
Background： Many studies have suggested that cigarette smoking and polymorphisms of resi stin and glutathione peroxidase-1 （GPx-1） genes are closely correlated with tile pathogenesis of nonalcoholic lhtty liver dis...Background： Many studies have suggested that cigarette smoking and polymorphisms of resi stin and glutathione peroxidase-1 （GPx-1） genes are closely correlated with tile pathogenesis of nonalcoholic lhtty liver disease （NAFLD）. However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, exalnined the distribution of polymorphisms in GPx-l and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status. Methods： Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter- 420C/G and GPx- 1 gene Pro 198Leu were analyzed by polymorphism-polymerase chain reaction （PCR） in DNA extracted from peripheral blood leukocytes. Interactions between tile two mutants and the gene-environment interaction with cigarette smoking were also analyzed. Results： Genotype frequencies of 420C/G （GG） and Pro198Leu （LL） were significantly higher in NAFLD cases （49.56% and 50.11%, respectively） compared with healthy controls （23.67% and 24.22%, respectively） （P = 0.0069： P= 0.0072）. Moreover, the risk of NAFLD with 420C/G （GGJ was significantly higher than in controls （odds ratio [OR] =3.1685, 95% confidence interval （（7） 1.9366-5.2073）. Individuals carrying Pro198Leu （LL） had a high risk of NAFLD （OR - 3.1424, 95% C/= 1.7951 5.2367）. Combined analysis of the polymorphisms showed that the -420C/G （GG）/Pro198Leu （LL） genotype was significantly more common in the NAFLD group than in the control group （39.44% vs. 12.78%, respectively, P 0.0054）, while individuals with -420C/G （GG）/Pro198Leu （LL） had a high risk of NAFLD （OR = 5.（1357, 95% CI= 3.1852 7.8106）. Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in tile control group （OR = 1.8990, P = 0.0083 in the smoking index （SI） _〈400 subgroup： OR = 5.0937, P = 0.0051 in the SI 〉400 subgroup）, and statistical analysis suggested a positive interaction between cigarette smoking and 420C/G （GG） （y = 5.6018 in tile SI≤400 subgroup; γ - 4.4770 in the SI 〉400 subgroup） and Pro198Leu （LL） （y = 5.7715 in the SI ≤400 subgroup： γ 4.5985 in the SI 〉400 subgroup） in increasing the risk of NAFLD. Conclusion： NAFLD risk factors include -420C/G （GG）, Pro198Leu （LL） and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.展开更多
文摘GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI contributes to at least fifty percent of GPX activity in rodent small intestmal epithelium. The total GPX activity consists of at least 70% of selenium-dependent GPX activity in this compartment.By analyzing a panel of mouse mterspecies DNA from the Jackson Laboratory's backcross resource,we mapped Gpx2 gene to mouse chromosome 12 between D12Mit4 and D12Mit5, near the Ccs1 locus which contains a colon cancer susceptibility gene. A pseudogene, Gpx2-ps is mapped to mouse chromosome 7.Comparison of Gpx2 gene expression in three pairs of C57BL/6Ha and ICR/Ha mice which are respectively resistant and sensitive to dimethylhydrazine-induced colon cancer, we found a higher Gpx2 mRNA level in C57BL/6Ha colon than ICR/Ha colon. Interestingly, a lower level of GPX activity is found in the resistant strain of mice. Because GPX-1 has three times higher specific activity than GPX GI, our data suggest that the decreased GPX activity may result from a higher level of Gpx2 gene expression in those cells co-express GPx1 gene
文摘In the blood fluke Schistosoma mansoni a functionally active, monomeric, phospholipid hydroperoxide glutathione peroxidase (PHGPx) has been purified and characterized. This enzyme contains a catalytically active selenocysteine. The protein has been shown to be the product of a cloned gene, previously referred to as a glutathione peroxidase gene. S. mansoni PHGPx has been found 5 times more abundant in female than in male worm extract. As in vertebrate PHGPx, homology alignment indicates that the residues involved in the glutathione binding by the tetrameric cellular glutathione peroxidase are mutated in the S. mansoni enzyme. Thus, this aspect appears a landmark of the PHGPx-type of glutathione peroxidases,which might be of functional relevance
文摘We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was signiifcantly enhanced in the model group. Af-ter 8 weeks, the number of horseradish peroxidase-labeled nerve ifbers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and signiifcantly higher than in the model group. The newly formed nerve ifbers and myelinated ner ve ifbers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant no.31900310 to R.T.)the Key Project of the National Natural Science Foundation of China(NSFC)(Grant no.31630071 to G.Y.)+1 种基金the National Natural Science Foundation of China(NSFC)(Grant no.31950410545 to I.S.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘The molecular basis for adaptations to extreme environments can now be understood by interrogating the everincreasing number of sequenced genomes.Mammals such as cetaceans,bats,and highland species can protect themselves from oxidative stress,a disruption in the balance of reactive oxygen species,which results in oxidative injury and cell damage.Here,we consider the evolution of the glutathione peroxidase(GPX)family of antioxidant enzymes by interrogating publicly available genome data from 70 mammalian species from all major clades.We identified 8 GPX subclasses ubiquitous to all mammalian groups.Mammalian GPX gene families resolved into the GPX4/7/8 and GPX1/2/3/5/6 groups and are characterized by several instances of gene duplication and loss,indicating a dynamic process of gene birth and death in mammals.Seven of the eight GPX subfamilies(all but GPX7)were under positive selection,with the residues under selection located at or close to active sites or at the dimer interface.We also reveal evidence of a correlation between ecological niches(e.g.high oxidative stress)and the divergent selection and gene copy number of GPX subclasses.Notably,a convergent expansion of GPX1 was observed in several independent lineages of mammals under oxidative stress and may be important for avoiding oxidative damage.Collectively,this study suggests that the GPX gene family has shaped the adaption of mammals to stressful environments.
文摘Background： Many studies have suggested that cigarette smoking and polymorphisms of resi stin and glutathione peroxidase-1 （GPx-1） genes are closely correlated with tile pathogenesis of nonalcoholic lhtty liver disease （NAFLD）. However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, exalnined the distribution of polymorphisms in GPx-l and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status. Methods： Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter- 420C/G and GPx- 1 gene Pro 198Leu were analyzed by polymorphism-polymerase chain reaction （PCR） in DNA extracted from peripheral blood leukocytes. Interactions between tile two mutants and the gene-environment interaction with cigarette smoking were also analyzed. Results： Genotype frequencies of 420C/G （GG） and Pro198Leu （LL） were significantly higher in NAFLD cases （49.56% and 50.11%, respectively） compared with healthy controls （23.67% and 24.22%, respectively） （P = 0.0069： P= 0.0072）. Moreover, the risk of NAFLD with 420C/G （GGJ was significantly higher than in controls （odds ratio [OR] =3.1685, 95% confidence interval （（7） 1.9366-5.2073）. Individuals carrying Pro198Leu （LL） had a high risk of NAFLD （OR - 3.1424, 95% C/= 1.7951 5.2367）. Combined analysis of the polymorphisms showed that the -420C/G （GG）/Pro198Leu （LL） genotype was significantly more common in the NAFLD group than in the control group （39.44% vs. 12.78%, respectively, P 0.0054）, while individuals with -420C/G （GG）/Pro198Leu （LL） had a high risk of NAFLD （OR = 5.（1357, 95% CI= 3.1852 7.8106）. Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in tile control group （OR = 1.8990, P = 0.0083 in the smoking index （SI） _〈400 subgroup： OR = 5.0937, P = 0.0051 in the SI 〉400 subgroup）, and statistical analysis suggested a positive interaction between cigarette smoking and 420C/G （GG） （y = 5.6018 in tile SI≤400 subgroup; γ - 4.4770 in the SI 〉400 subgroup） and Pro198Leu （LL） （y = 5.7715 in the SI ≤400 subgroup： γ 4.5985 in the SI 〉400 subgroup） in increasing the risk of NAFLD. Conclusion： NAFLD risk factors include -420C/G （GG）, Pro198Leu （LL） and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.
