Astrocytes play a major role in the reactive processes in response to neuronal injuries in the brain. Excessive gliosis is detrimental and can contribute to neuronal damage. CDS1 （TAPA）, a member of the tetraspanin ...Astrocytes play a major role in the reactive processes in response to neuronal injuries in the brain. Excessive gliosis is detrimental and can contribute to neuronal damage. CDS1 （TAPA）, a member of the tetraspanin family of proteins, is upregulated by astrocytes after traumatic injury to the rat central nervous system （CNS）. To further understand the role of CD81 in the inhibition of astrocytes, we analyzed the effects of a CD81 antibody, on cultured rat astrocytes. The results indicated that the effect worked in a dose-dependent manner with certain dosage range. It, however, reached a dosage equilibrium at a high dosage. Furthermore, anti-CD81 antibody remarkably inhibited the proliferation of astrocytes after incubation with astrocytes for different periods of time and the effect presented a time-dependent fashion. However, anti-CDS1 antibody substantially inhibited the proliferation of astrocytes at low density and middle density but slightly inhibited the proliferation of as- trocytes at high density, suggesting that the effect was positively correlated with the proliferative ability of astrocytes. Finally, the cell cycle of astrocytes exposured to anti-CD81 antibody was arrested in S phase at the initial stage and at G0/GI phase over time. These findings indicated that CD81 exert significant inhibitory effect, dose-dependently and time-dependently, on the proliferation of astrocytes and the effect is positively correlated with the proliferative capability of astrocytes.展开更多
There are 33 human tetraspanin proteins,emerging as key players in malignancy,the immune system,fertilization,cellular signaling,adhesion,morphology,motility,proliferation,and tumor invasion.CD9,a member of the tetras...There are 33 human tetraspanin proteins,emerging as key players in malignancy,the immune system,fertilization,cellular signaling,adhesion,morphology,motility,proliferation,and tumor invasion.CD9,a member of the tetraspanin family,associates with and influences a variety of cell-surface molecules.Through these interactions,CD9 modifies multiple cellular events,including adhesion,migration,proliferation,and survival.CD9 is therefore considered to play a role in several stages during cancer development.Reduced CD9 expression is generally related to venous vessel invasion and metastasis as well as poor prognosis.We found that treatment of mice bearing human gastric cancer cells with anti-CD9 antibody successfully inhibited tumor progression via antiproliferative,proapoptotic,and antiangiogenic effects,strongly indicating that CD9 is a possible therapeutic target in patients with gastric cancer.Here,we describe the possibility of CD9 manipulation as a novel therapeutic strategy in gastric cancer,which still shows poor prognosis.展开更多
Objective:To identify a full length cDNA sequence of a novel tetraspanin(TSP) homologue from Spirometra erinaceieuropaei and to predict the structure and function of its encoding protein using bioinformatics methods.M...Objective:To identify a full length cDNA sequence of a novel tetraspanin(TSP) homologue from Spirometra erinaceieuropaei and to predict the structure and function of its encoding protein using bioinformatics methods.Methods:Using the NCBI,EMBI,Expasy and other online sites, the open reading frame(ORF),conserved domain,physical and chemical parameters,signal peptide,transmembrane domain,epitope,topological structures of the protein sequences were predicted.And Vector NTI software was used for multiple sequence alignment and phylogenetic tree construction.Results:’Hie target sequence was 1 132 hp length with a 681 hp biggest ORF encoding 226 amino acids protein with typical TSP conserved domain.It was confirmed as full length cDNA of TSP16 from Spirometra erinaceieuropaei and named as SeTSP16 (GenBank accession number:JF728872).The predicted molecular weight and isoelectric point of the deduced protein were 24 750.5 Da and 7.88 Da,respectively.Compared with TSP16s from Schistosoma japonicum and Schistosoma mansoni.it showed similarity of 59%and 59%, respectively.SeTSP16 contained four transmembrane domains(TM 1-4),intracellular N and C-termini,one short small extracellular loop and one large extracellular loop.Four major epitopes that were significant different from the corresponding epitope regions of TSP16 from Schistosoma mansoni and Schistosoma japonicum were predicted.Conclusions:The full length cDNA sequences of SeTSP16 arc identified.It encodes a transmembrane protein which might be an ideal diagnosis antigen and target molecule for antiparasitic drugs.展开更多
This study characterized the activation of platelet integrin α bβ3 induced by two anti human platelet tetraspanin monoclonal antibodies(mAbs),HI117 and SJ9A4. Methods.Using 125 I labeled human fibrinogen(Fg),specifi...This study characterized the activation of platelet integrin α bβ3 induced by two anti human platelet tetraspanin monoclonal antibodies(mAbs),HI117 and SJ9A4. Methods.Using 125 I labeled human fibrinogen(Fg),specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured as indication of activation of platelet integrin αbβ3 by the two mAbs. Results.HI117 and SJ9A4(10μg/ml and 20μg/ml) induced evident specific Fg binding to human platelets,suggesting that the two mAbs evoked activation of platelet integrin αbβ3.Further study indicated that HI117 and SJ9A4 induced integrin αⅡbβ3 activation independent of platelet Fc receptors, and that HI117 and SJ9A4 induced integrin αbβ3 activation was inhibited by sphingosing, aspirin, apyrase, and/or PGI2. Conclusion.The anti platelet tetraspanin(CD9)mAbs,HI117 and SJ9A4, can induce platelet integrin αⅡbβ3 activation independent of Fc receptors.Three signaling pathways,i.e.thromboxane,secreted ADP, and cAMP pathways may be involved in the process,with protein kinase C activation presumably being the common step of the three pathways.展开更多
Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic contexts.It is thus ...Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic contexts.It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms.Methods:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution etc.Results:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal TM4SF5.Proximity labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and autophagy.TM4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-oxidation.In mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver malignancy.Conclusions:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.展开更多
characterize the activation of platelet integrin αⅡbβ3 induced by two anti human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4, and investigate their potential mechanism of action Method...characterize the activation of platelet integrin αⅡbβ3 induced by two anti human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4, and investigate their potential mechanism of action Methods Using 125 I labeled human fibrinogen (Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured Results HI117 and SJ9A4 (10?μg/ml and 20?μg/ml) induced specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin αⅡbβ3 Further study indicated that HI117 and SJ9A4 induced integrin αⅡbβ3 activation independent of platelet Fc receptors, and that HI117 and SJ9A4 induced integrin αⅡbβ3 activation was inhibited by pretreatment of platelets with sphingosine, aspirin, apyrase, and/or PGI 2 Conclusions Anti platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin αⅡbβ3 activation independent of Fc receptors Three signaling pathways, namely thromboxane, secreted ADP, and cAMP pathways, may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways展开更多
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30570568)
文摘Astrocytes play a major role in the reactive processes in response to neuronal injuries in the brain. Excessive gliosis is detrimental and can contribute to neuronal damage. CDS1 （TAPA）, a member of the tetraspanin family of proteins, is upregulated by astrocytes after traumatic injury to the rat central nervous system （CNS）. To further understand the role of CD81 in the inhibition of astrocytes, we analyzed the effects of a CD81 antibody, on cultured rat astrocytes. The results indicated that the effect worked in a dose-dependent manner with certain dosage range. It, however, reached a dosage equilibrium at a high dosage. Furthermore, anti-CD81 antibody remarkably inhibited the proliferation of astrocytes after incubation with astrocytes for different periods of time and the effect presented a time-dependent fashion. However, anti-CDS1 antibody substantially inhibited the proliferation of astrocytes at low density and middle density but slightly inhibited the proliferation of as- trocytes at high density, suggesting that the effect was positively correlated with the proliferative ability of astrocytes. Finally, the cell cycle of astrocytes exposured to anti-CD81 antibody was arrested in S phase at the initial stage and at G0/GI phase over time. These findings indicated that CD81 exert significant inhibitory effect, dose-dependently and time-dependently, on the proliferation of astrocytes and the effect is positively correlated with the proliferative capability of astrocytes.
文摘There are 33 human tetraspanin proteins,emerging as key players in malignancy,the immune system,fertilization,cellular signaling,adhesion,morphology,motility,proliferation,and tumor invasion.CD9,a member of the tetraspanin family,associates with and influences a variety of cell-surface molecules.Through these interactions,CD9 modifies multiple cellular events,including adhesion,migration,proliferation,and survival.CD9 is therefore considered to play a role in several stages during cancer development.Reduced CD9 expression is generally related to venous vessel invasion and metastasis as well as poor prognosis.We found that treatment of mice bearing human gastric cancer cells with anti-CD9 antibody successfully inhibited tumor progression via antiproliferative,proapoptotic,and antiangiogenic effects,strongly indicating that CD9 is a possible therapeutic target in patients with gastric cancer.Here,we describe the possibility of CD9 manipulation as a novel therapeutic strategy in gastric cancer,which still shows poor prognosis.
文摘Objective:To identify a full length cDNA sequence of a novel tetraspanin(TSP) homologue from Spirometra erinaceieuropaei and to predict the structure and function of its encoding protein using bioinformatics methods.Methods:Using the NCBI,EMBI,Expasy and other online sites, the open reading frame(ORF),conserved domain,physical and chemical parameters,signal peptide,transmembrane domain,epitope,topological structures of the protein sequences were predicted.And Vector NTI software was used for multiple sequence alignment and phylogenetic tree construction.Results:’Hie target sequence was 1 132 hp length with a 681 hp biggest ORF encoding 226 amino acids protein with typical TSP conserved domain.It was confirmed as full length cDNA of TSP16 from Spirometra erinaceieuropaei and named as SeTSP16 (GenBank accession number:JF728872).The predicted molecular weight and isoelectric point of the deduced protein were 24 750.5 Da and 7.88 Da,respectively.Compared with TSP16s from Schistosoma japonicum and Schistosoma mansoni.it showed similarity of 59%and 59%, respectively.SeTSP16 contained four transmembrane domains(TM 1-4),intracellular N and C-termini,one short small extracellular loop and one large extracellular loop.Four major epitopes that were significant different from the corresponding epitope regions of TSP16 from Schistosoma mansoni and Schistosoma japonicum were predicted.Conclusions:The full length cDNA sequences of SeTSP16 arc identified.It encodes a transmembrane protein which might be an ideal diagnosis antigen and target molecule for antiparasitic drugs.
文摘This study characterized the activation of platelet integrin α bβ3 induced by two anti human platelet tetraspanin monoclonal antibodies(mAbs),HI117 and SJ9A4. Methods.Using 125 I labeled human fibrinogen(Fg),specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured as indication of activation of platelet integrin αbβ3 by the two mAbs. Results.HI117 and SJ9A4(10μg/ml and 20μg/ml) induced evident specific Fg binding to human platelets,suggesting that the two mAbs evoked activation of platelet integrin αbβ3.Further study indicated that HI117 and SJ9A4 induced integrin αⅡbβ3 activation independent of platelet Fc receptors, and that HI117 and SJ9A4 induced integrin αbβ3 activation was inhibited by sphingosing, aspirin, apyrase, and/or PGI2. Conclusion.The anti platelet tetraspanin(CD9)mAbs,HI117 and SJ9A4, can induce platelet integrin αⅡbβ3 activation independent of Fc receptors.Three signaling pathways,i.e.thromboxane,secreted ADP, and cAMP pathways may be involved in the process,with protein kinase C activation presumably being the common step of the three pathways.
基金This work was supported by Basic Science Research Pro-gram through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2021R1A6A3A01087300 to JEK,NRF-2021M3H9A2098553 to YL,NRF-2022M3E5F3080873 to SC,NRF-2022R1A4A1018900 to LKH,NRF-2020R1A2C3008993,and NRF-2021M3A9D3024752 to JWL).
文摘Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic contexts.It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms.Methods:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution etc.Results:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal TM4SF5.Proximity labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and autophagy.TM4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-oxidation.In mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver malignancy.Conclusions:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.
基金grantfromtheNationalNaturalScienceFoundationofChina (No 39470 172 )
文摘characterize the activation of platelet integrin αⅡbβ3 induced by two anti human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4, and investigate their potential mechanism of action Methods Using 125 I labeled human fibrinogen (Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured Results HI117 and SJ9A4 (10?μg/ml and 20?μg/ml) induced specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin αⅡbβ3 Further study indicated that HI117 and SJ9A4 induced integrin αⅡbβ3 activation independent of platelet Fc receptors, and that HI117 and SJ9A4 induced integrin αⅡbβ3 activation was inhibited by pretreatment of platelets with sphingosine, aspirin, apyrase, and/or PGI 2 Conclusions Anti platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin αⅡbβ3 activation independent of Fc receptors Three signaling pathways, namely thromboxane, secreted ADP, and cAMP pathways, may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways
