Protein S-nitrosation(SNO),an essential posttranslational modification(PTM)elicited by nitric oxide(NO)1,regulates a broad range of physiological/pathological processes2.Recently,a study led by Jonathan Stamler3 publi...Protein S-nitrosation(SNO),an essential posttranslational modification(PTM)elicited by nitric oxide(NO)1,regulates a broad range of physiological/pathological processes2.Recently,a study led by Jonathan Stamler3 published in Cell explores the discovery and characterization of an enzyme that selectively S-nitrosylates proteins to regulate insulin signaling.展开更多
S-Nitros(yl)ation is a ubiquitous redox-based post-translational modification of protein cysteine thiols by nitric oxide or its derivatives,which transduces the bioactivity of nitric oxide(NO)by regulation of protein ...S-Nitros(yl)ation is a ubiquitous redox-based post-translational modification of protein cysteine thiols by nitric oxide or its derivatives,which transduces the bioactivity of nitric oxide(NO)by regulation of protein conformation,activity,stability,localization and pro-tein-protein interactions.These years,more and more S-nitrosated proteins were identified in physiological and pathological processes and the number is still growing.Here we developed a database named SNO-base(http://www.nitrosation.org),which collected S-nitrosation targets extracted from literatures up to June 1st,2012.SNObase contained 2561 instances,and provided information about S-nitrosation targets,sites,biological model,related diseases,trends of S-nitrosation level and effects of S-nitrosation on protein function.With SNObase,we did functional analysis for all the SNO targets:In the gene ontology(GO)biological process category,some processes were discovered to be related to S-nitrosation(“response to drug”,“regulation of cell motion”)besides the previously reported related processes.In the GO cellular component category,cytosol and mitochondrion were both enriched.From the KEGG pathway enrichment results,we found SNO targets were enriched in different diseases,which suggests possible significant roles of S-nitrosation in the progress of these diseases.This SNObase means to be a database with precise,comprehensive and easily accessible information,an environment to help researchers integrate data with comparison and relevancy analysis between different groups or works,and also an SNO knowledgebase offering feasibility for systemic and global analysis of S-nitrosation in interdisciplinary studies.展开更多
Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases.However,the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unkn...Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases.However,the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown.In this study,we demonstrated that S-nitrosoglutathione reductase(GSNOR)deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1βexpression levels and interleukin-1β(IL-1β)secretion in response to NLRP3 inflammasome stimulation.Furthermore,in vivo experiments utilizing Gsnor^(−/−)mice revealed increased disease severity in both lipopolysaccharide(LPS)-induced septic shock and dextran sodium sulfate(DSS)-induced colitis models.Additionally,we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor^(−/−)Nlrp3^(−/−)double-knockout(DKO)mice.Mechanistically,GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14(MAPK14)at the Cys211 residue and augments MAPK14 kinase activity,thereby promoting Nlrp3 and Il-1βtranscription and stimulating NLRP3 inflammasome activity.Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.展开更多
Nitric oxide(NO)and hydrogen sulfide(HS)are two molecules that share signaling properties in plant and animal cells NO and H2S originate two farmilies of de rived mol ecules designated reactive nitrogen and sulfur spe...Nitric oxide(NO)and hydrogen sulfide(HS)are two molecules that share signaling properties in plant and animal cells NO and H2S originate two farmilies of de rived mol ecules designated reactive nitrogen and sulfur species(RNS and RSS,respectively).These molecules are responsible for certain protein regulatory processes through posttranslational modifications(PTMs),being the most remarkable S nitrosation and persufidation,which afect the thiol group of cysteine residues.NO and H2S can also exert regulatory functions due to their interaction through the iron present in proteins that contain heme groups or iron-sulfur dlusters,as reported mainly in animal cells.Howewer,the available information in plant cells is still very limited thus far.In higher plants,NO and H2S are involved in a myriad of physiological events from seed germination to fruit ripening,but also the mec hanism of response to biotic and abiotic stress conditions.This vie wpoint manuscript highlights the functional regulatory parllelism of these two molecules which also interact with the metabolism of reactive oxygen species(ROS)in plant cells.展开更多
In this study we developed a quantitative proteomic method named ICATswitch by introducing isotope-coded affinity tag(ICAT)reagents into the biotin-switch method,and used it to investigate S-nitrosation in the liver o...In this study we developed a quantitative proteomic method named ICATswitch by introducing isotope-coded affinity tag(ICAT)reagents into the biotin-switch method,and used it to investigate S-nitrosation in the liver of normal control C57BL/6J mice and type 2 diabetic KK-Ay mice.We got fifty-eight S-nitrosated peptides with quantitative information in our research,among which thirty-seven had changed S-nitrosation levels in diabetic mouse liver.The S-nitrosated peptides belonged to fortyeight proteins(twenty-eight were new S-nitrosated proteins),some of which were new targets of S-nitrosation and known to be related with diabetes.S-nitrosation patterns were different between diabetic and normal mice.Gene ontology enrichment results suggested that S-nitrosated proteins are more abundant in amino acid metabolic processes.The network constructed for Snitrosated proteins by text-mining technology provided clues about the relationship between S-nitrosation and type 2 diabetes.Our work provides a new approach for quantifying S-nitrosated proteins and suggests that the integrative functions of S-nitrosation may take part in pathophysiological processes of type 2 diabetes.展开更多
Nitric oxide(NO)participates in various pathways and revealing its dynamics is critical for resolving its pathophysiology.While there are methods available for detecting biological NO,few are capable of tracking NO dy...Nitric oxide(NO)participates in various pathways and revealing its dynamics is critical for resolving its pathophysiology.While there are methods available for detecting biological NO,few are capable of tracking NO dynamics.Herein,inspired by the cellular machinery of reversible thiol modification by NO,we have successfully designed a family of cysteine analogues tagged with fluorophores for visualizing cellular NO dynamics.展开更多
基金supported by grants from the Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01D38 and 2023D01D16,China)the National Natural Science Foundation of China(No.82473773,82173681,82104004 and 82273780)+3 种基金the Key Research and Development Program of Xinjiang Uygur Autonomous Region(2023B03012-1,China)the Prevention and Treatment of High Incidence Diseases in Central Asia Fund(SKL-HIDCA-2024-4,China)the Fundamental Research Funds for the Central Universities of China Pharmaceutical University(No.2632023TD04,China)the“Double First-Class”University projects(CPU2022PZQ15 from China Pharmaceutical University,China).
文摘Protein S-nitrosation(SNO),an essential posttranslational modification(PTM)elicited by nitric oxide(NO)1,regulates a broad range of physiological/pathological processes2.Recently,a study led by Jonathan Stamler3 published in Cell explores the discovery and characterization of an enzyme that selectively S-nitrosylates proteins to regulate insulin signaling.
基金supported by the National Basic Research Program of China(973 Program)(Nos.2011CB910900,2012CB911000,2011CB503900)the National Natural Sciences Foundation of China(Grant No.31030023)the Knowledge Innovation Program of the Chinese Academy of Sciences.
文摘S-Nitros(yl)ation is a ubiquitous redox-based post-translational modification of protein cysteine thiols by nitric oxide or its derivatives,which transduces the bioactivity of nitric oxide(NO)by regulation of protein conformation,activity,stability,localization and pro-tein-protein interactions.These years,more and more S-nitrosated proteins were identified in physiological and pathological processes and the number is still growing.Here we developed a database named SNO-base(http://www.nitrosation.org),which collected S-nitrosation targets extracted from literatures up to June 1st,2012.SNObase contained 2561 instances,and provided information about S-nitrosation targets,sites,biological model,related diseases,trends of S-nitrosation level and effects of S-nitrosation on protein function.With SNObase,we did functional analysis for all the SNO targets:In the gene ontology(GO)biological process category,some processes were discovered to be related to S-nitrosation(“response to drug”,“regulation of cell motion”)besides the previously reported related processes.In the GO cellular component category,cytosol and mitochondrion were both enriched.From the KEGG pathway enrichment results,we found SNO targets were enriched in different diseases,which suggests possible significant roles of S-nitrosation in the progress of these diseases.This SNObase means to be a database with precise,comprehensive and easily accessible information,an environment to help researchers integrate data with comparison and relevancy analysis between different groups or works,and also an SNO knowledgebase offering feasibility for systemic and global analysis of S-nitrosation in interdisciplinary studies.
基金Yunnan Fundamental Research Project(202305AH340006)National Natural Science Foundation of China(32201018)+1 种基金Basic Research Program and Key Project of Yunnan Province(202301AW070013 and 202003AD150009)Youth Innovation Promotion Association(2023403).
文摘Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases.However,the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown.In this study,we demonstrated that S-nitrosoglutathione reductase(GSNOR)deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1βexpression levels and interleukin-1β(IL-1β)secretion in response to NLRP3 inflammasome stimulation.Furthermore,in vivo experiments utilizing Gsnor^(−/−)mice revealed increased disease severity in both lipopolysaccharide(LPS)-induced septic shock and dextran sodium sulfate(DSS)-induced colitis models.Additionally,we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor^(−/−)Nlrp3^(−/−)double-knockout(DKO)mice.Mechanistically,GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14(MAPK14)at the Cys211 residue and augments MAPK14 kinase activity,thereby promoting Nlrp3 and Il-1βtranscription and stimulating NLRP3 inflammasome activity.Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.
基金supported by a European Regional Development Fund cofinanced grant from the Spanish Ministry of Science and Innovation(PID2019-103924GB-100)the Plan Andaluz de Investigacion,Desarrollo e Innovacion(PAIDI 2020)(P18-FR-1359)Junta de Andalucla(Group BIO192),Spain.
文摘Nitric oxide(NO)and hydrogen sulfide(HS)are two molecules that share signaling properties in plant and animal cells NO and H2S originate two farmilies of de rived mol ecules designated reactive nitrogen and sulfur species(RNS and RSS,respectively).These molecules are responsible for certain protein regulatory processes through posttranslational modifications(PTMs),being the most remarkable S nitrosation and persufidation,which afect the thiol group of cysteine residues.NO and H2S can also exert regulatory functions due to their interaction through the iron present in proteins that contain heme groups or iron-sulfur dlusters,as reported mainly in animal cells.Howewer,the available information in plant cells is still very limited thus far.In higher plants,NO and H2S are involved in a myriad of physiological events from seed germination to fruit ripening,but also the mec hanism of response to biotic and abiotic stress conditions.This vie wpoint manuscript highlights the functional regulatory parllelism of these two molecules which also interact with the metabolism of reactive oxygen species(ROS)in plant cells.
基金supported by the National Basic Research Program(973 program)of China(Grant Nos.2006CB911001,2005CB522804)the National Natural Science Foundation of China(Grant Nos.90606020 and 30770512)the Knowledge Innovation Program of the Chinese Academy of Sciences.
文摘In this study we developed a quantitative proteomic method named ICATswitch by introducing isotope-coded affinity tag(ICAT)reagents into the biotin-switch method,and used it to investigate S-nitrosation in the liver of normal control C57BL/6J mice and type 2 diabetic KK-Ay mice.We got fifty-eight S-nitrosated peptides with quantitative information in our research,among which thirty-seven had changed S-nitrosation levels in diabetic mouse liver.The S-nitrosated peptides belonged to fortyeight proteins(twenty-eight were new S-nitrosated proteins),some of which were new targets of S-nitrosation and known to be related with diabetes.S-nitrosation patterns were different between diabetic and normal mice.Gene ontology enrichment results suggested that S-nitrosated proteins are more abundant in amino acid metabolic processes.The network constructed for Snitrosated proteins by text-mining technology provided clues about the relationship between S-nitrosation and type 2 diabetes.Our work provides a new approach for quantifying S-nitrosated proteins and suggests that the integrative functions of S-nitrosation may take part in pathophysiological processes of type 2 diabetes.
基金supported by the National Natural Science Foundations of China(nos.22077112,21778048,81673489,31871414,and 81125023)Natural Science Foundation of Zhejiang Province,China(no.LR18H300001)National Science and Technology Major Project“Key New Drug Creation and Manufacturing Program”(nos.2018ZX09711002-010-004,2018ZX09711002-007-002,2019ZX09201001-003-009,2019ZX09201001-003-010,and 2019ZX09201001-004-010),K.C.Wong Education Foundation,and Singapore University of Technology and Design(SUTD)[SUTD-ZJU IDEA grant nos.T1SRCI17126 and SUTD-ZJU(VP)201905].
文摘Nitric oxide(NO)participates in various pathways and revealing its dynamics is critical for resolving its pathophysiology.While there are methods available for detecting biological NO,few are capable of tracking NO dynamics.Herein,inspired by the cellular machinery of reversible thiol modification by NO,we have successfully designed a family of cysteine analogues tagged with fluorophores for visualizing cellular NO dynamics.
