Osmotic stress caused by drought and high salinity is a significant environmental threat that limits plant growth and agricultural yield. Redox regulation plays an important role in plant stress responses, but the mec...Osmotic stress caused by drought and high salinity is a significant environmental threat that limits plant growth and agricultural yield. Redox regulation plays an important role in plant stress responses, but the mechanisms by which plants perceive and transduce redox signals are still underexplored. Here, we report a critical function for the thiol peroxidase GPX1 in osmotic stress response in rice, where it serves as a redox sensor and transducer. GPX1 is quickly oxidized upon exposure to osmotic stress and forms an intramolecular disulfide bond, which is required for the activation of bZIP68, a VRE-like basic leucine zipper (bZIP) transcription factor involved in the ABA-independent osmotic stress response pathway. The disulfide exchange between GPX1 and bZIP68 induces homo-tetramerization of bZIP68 and thus positively regulates osmotic stress response by regulating osmotic-responsive gene expression. Furthermore, we discovered that the nuclear translocation of GPX1 is regulated by its acetylation under osmotic stress. Taken together, our findings not only uncover the redox regulation of the GPX1-bZIP68 module during osmotic stress but also highlight the coordination of protein acetylation and redox signaling in plant osmotic stress responses.展开更多
Over-accumulation of reactive oxygen species(ROS)causes mitochondrial dysfunction and impairs the osteogenic potential of bone marrow-derived mesenchymal stem cells(BMMSCs).Selenium(Se)protects BMMSCs from oxidative s...Over-accumulation of reactive oxygen species(ROS)causes mitochondrial dysfunction and impairs the osteogenic potential of bone marrow-derived mesenchymal stem cells(BMMSCs).Selenium(Se)protects BMMSCs from oxidative stress-induced damage;however,it is unknown whether Se supplementation can promote the repair of osteoporotic bone defects by rescuing the impaired osteogenic potential of osteoporotic BMMSCs(OP-BMMSCs).In vitro treatment with sodium selenite(Na2SeO3)successfully improved the osteogenic differentiation of OP-BMMSCs,as demonstrated by increased matrix mineralization and up-regulated osteogenic genes expression.More importantly,Na2SeO3 restored the impaired mitochondrial functions of OP-BMMSCs,significantly up-regulated glutathione peroxidase 1(GPx1)expression and attenuated the intracellular ROS and mitochondrial superoxide.Silencing of Gpx1 completely abrogated the protective effects of Na2SeO3 on mitochondrial functions of OP-BMMSCs,suggesting the important role of GPx1 in protecting OP-BMMSCs from oxidative stress.We further fabricated Se-modified bone cement based on silk fibroin and calcium phosphate cement(SF/CPC).After 8 weeks of implantation,Se-modified bone cement significantly promoted bone defect repair,evidenced by the increased new bone tissue formation and enhanced GPx1 expression in ovariectomized rats.These findings revealed that Se supplementation rescued mitochondrial functions of OP-BMMSCs through activation of the GPx1-mediated antioxidant pathway,and more importantly,supplementation with Se in SF/CPC accelerated bone regeneration in ovariectomized rats,representing a novel strategy for treating osteoporotic bone fractures or defects.展开更多
Objective To construct and identify the Gpx1-Klk1 vector which contains kidney-specific promoter (Ksp-cadherin). Methods Through PCR amplification, the human Gpx1, Klk1, and Ksp-cadherin cDNA were obtained by taking G...Objective To construct and identify the Gpx1-Klk1 vector which contains kidney-specific promoter (Ksp-cadherin). Methods Through PCR amplification, the human Gpx1, Klk1, and Ksp-cadherin cDNA were obtained by taking Gpx1 cDNA, Klk1 cDNA, and Ksp-cadherin BAC as templates. After being testified, the PCR products were inserted into the expressive vector pIRES-EGFP step-by-step to produce a recombinant vector Ksp-cadherin-Gpx1-Klk1. This vector was examined by restriction enzyme digestion and sequence analysis. Results The recombinant expressive vector Ksp-cadherin-Gpx1-Klk1 was successfully constructed. Conclusion The construction of the recombinant vector Ksp-cadherin-Gpx1-Klk1 laid foundations for investigations in establishing transgenic animal models, the over-expression of Gpx1 and Klk1 in mammal kidney, and gene therapy for ischemia-reperfusion injury during kidney transplantation.展开更多
Thalassemia is associated with low antioxidant enzyme deficiency especially glutathione peroxidase. GPX exists in 6 isomeric forms out of which GPX1 Single Nucleotide Polymorphism is found to be associated with Thalas...Thalassemia is associated with low antioxidant enzyme deficiency especially glutathione peroxidase. GPX exists in 6 isomeric forms out of which GPX1 Single Nucleotide Polymorphism is found to be associated with Thalassemia major. In our study, the determination of the allelic frequency and phenotype of a common polymorphism in Se-dependent glutathione peroxidase 1 (GPX1) was observed in Thalassemic populations. A proline/leucine variant occurs at position 197 close to the C-terminus of the protein. The genotypes encoding Pro/Pro, Pro/Leu, and Leu/ Leu are distributed according to the Hardy-Weinberg relationship. The study has been carried out in 40 Thalassemic cases and 40 control subjects. No significant association between allele frequency and risk to get fatal was evident. Erythrocyte GPX activity was determined and no significant differences were obtained between the genotypes. It can be concluded that the Pro/Leu genetic variation does not appear to compromise the defense against oxidative stress in red blood cells or to be associated with significant pathology.展开更多
基金supported by grants from the National Natural Science Foundation of Jiangsu Province(BK20200561)the National Natural Science Foundation of China(32101671 and 31670255)+3 种基金the National Natural Science Foundation of Jiangsu Province(BK20200282 and BK20161447)the National Science Fund for Outstanding Young Scholars(21922702)the China Postdoctoral Science Foundation(2019M661860)the Fundamental Research Funds for the Central Universities(KYZ201859).
文摘Osmotic stress caused by drought and high salinity is a significant environmental threat that limits plant growth and agricultural yield. Redox regulation plays an important role in plant stress responses, but the mechanisms by which plants perceive and transduce redox signals are still underexplored. Here, we report a critical function for the thiol peroxidase GPX1 in osmotic stress response in rice, where it serves as a redox sensor and transducer. GPX1 is quickly oxidized upon exposure to osmotic stress and forms an intramolecular disulfide bond, which is required for the activation of bZIP68, a VRE-like basic leucine zipper (bZIP) transcription factor involved in the ABA-independent osmotic stress response pathway. The disulfide exchange between GPX1 and bZIP68 induces homo-tetramerization of bZIP68 and thus positively regulates osmotic stress response by regulating osmotic-responsive gene expression. Furthermore, we discovered that the nuclear translocation of GPX1 is regulated by its acetylation under osmotic stress. Taken together, our findings not only uncover the redox regulation of the GPX1-bZIP68 module during osmotic stress but also highlight the coordination of protein acetylation and redox signaling in plant osmotic stress responses.
基金supported by the National Natural Science Foundation of China(82072476,82072410)Natural Science Foundation of Jiangsu Province(BK20220046)+2 种基金Major Science and Technology Project of Changzhou Health Commission(ZD202001)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)and Key Laboratory of Orthopaedics of Suzhou(SZS2022017).
文摘Over-accumulation of reactive oxygen species(ROS)causes mitochondrial dysfunction and impairs the osteogenic potential of bone marrow-derived mesenchymal stem cells(BMMSCs).Selenium(Se)protects BMMSCs from oxidative stress-induced damage;however,it is unknown whether Se supplementation can promote the repair of osteoporotic bone defects by rescuing the impaired osteogenic potential of osteoporotic BMMSCs(OP-BMMSCs).In vitro treatment with sodium selenite(Na2SeO3)successfully improved the osteogenic differentiation of OP-BMMSCs,as demonstrated by increased matrix mineralization and up-regulated osteogenic genes expression.More importantly,Na2SeO3 restored the impaired mitochondrial functions of OP-BMMSCs,significantly up-regulated glutathione peroxidase 1(GPx1)expression and attenuated the intracellular ROS and mitochondrial superoxide.Silencing of Gpx1 completely abrogated the protective effects of Na2SeO3 on mitochondrial functions of OP-BMMSCs,suggesting the important role of GPx1 in protecting OP-BMMSCs from oxidative stress.We further fabricated Se-modified bone cement based on silk fibroin and calcium phosphate cement(SF/CPC).After 8 weeks of implantation,Se-modified bone cement significantly promoted bone defect repair,evidenced by the increased new bone tissue formation and enhanced GPx1 expression in ovariectomized rats.These findings revealed that Se supplementation rescued mitochondrial functions of OP-BMMSCs through activation of the GPx1-mediated antioxidant pathway,and more importantly,supplementation with Se in SF/CPC accelerated bone regeneration in ovariectomized rats,representing a novel strategy for treating osteoporotic bone fractures or defects.
基金supported by the National Natural Science Foundation of China (No.30471640)
文摘Objective To construct and identify the Gpx1-Klk1 vector which contains kidney-specific promoter (Ksp-cadherin). Methods Through PCR amplification, the human Gpx1, Klk1, and Ksp-cadherin cDNA were obtained by taking Gpx1 cDNA, Klk1 cDNA, and Ksp-cadherin BAC as templates. After being testified, the PCR products were inserted into the expressive vector pIRES-EGFP step-by-step to produce a recombinant vector Ksp-cadherin-Gpx1-Klk1. This vector was examined by restriction enzyme digestion and sequence analysis. Results The recombinant expressive vector Ksp-cadherin-Gpx1-Klk1 was successfully constructed. Conclusion The construction of the recombinant vector Ksp-cadherin-Gpx1-Klk1 laid foundations for investigations in establishing transgenic animal models, the over-expression of Gpx1 and Klk1 in mammal kidney, and gene therapy for ischemia-reperfusion injury during kidney transplantation.
文摘Thalassemia is associated with low antioxidant enzyme deficiency especially glutathione peroxidase. GPX exists in 6 isomeric forms out of which GPX1 Single Nucleotide Polymorphism is found to be associated with Thalassemia major. In our study, the determination of the allelic frequency and phenotype of a common polymorphism in Se-dependent glutathione peroxidase 1 (GPX1) was observed in Thalassemic populations. A proline/leucine variant occurs at position 197 close to the C-terminus of the protein. The genotypes encoding Pro/Pro, Pro/Leu, and Leu/ Leu are distributed according to the Hardy-Weinberg relationship. The study has been carried out in 40 Thalassemic cases and 40 control subjects. No significant association between allele frequency and risk to get fatal was evident. Erythrocyte GPX activity was determined and no significant differences were obtained between the genotypes. It can be concluded that the Pro/Leu genetic variation does not appear to compromise the defense against oxidative stress in red blood cells or to be associated with significant pathology.
