BACKGROUND It is critical to explore effective therapeutic targets for improving the survival rate of patients with hepatocellular carcinoma(HCC).Although many studies have focused on flotillin-1(FLOT1)as a lipid raft...BACKGROUND It is critical to explore effective therapeutic targets for improving the survival rate of patients with hepatocellular carcinoma(HCC).Although many studies have focused on flotillin-1(FLOT1)as a lipid raft-associated protein that regulates the activation of some proteins or kinases to promote tumor cell survival and proliferation,few studies have explored the regulation of Golgi apparatus function.AIM To investigate the molecular mechanism through which FLOT1 activates the Golgi stress response downstream of transcription factor E3(TFE3),thereby promoting the progression of HCC.METHODS FLOT1 expression in HCC tissue,HCC cell lines,and nude mouse tumor models was assessed.The impact of FLOT1 silencing or its overexpression on the proliferation of HCC cells was studied.CCK-8,flow cytometry,and transwell assays were used to assess the proliferation,cell cycle,migration,and invasion abilities of HCC cells.A dual-luciferase reporter assay was used to study the effect of FLOT1 on the transcriptional activity of the downstream Golgi apparatus stress element promoter of TFE3.Western blotting,co-immunoprecipitation,and immunofluorescence staining were employed to detect relevant proteins.RESULTS High FLOT1 expression was correlated with a poor prognosis in patients with HCC.The knockdown of FLOT1 suppressed the proliferation,migration,and invasion of HCC cells and promoted their apoptosis.Xenograft assays revealed that FLOT1 knockdown inhibited HCC tumorigenesis in vivo.Mechanistically,FLOT1 inhibited the expression of mechanistic target of rapamycin complex 1/2 proteins through ubiquitination and downstream effector p-S6 kinase-T389,leading to the dephosphorylation and nuclear translocation of TFE3 and promotion of Golgi stress-mediated responses,ultimately resulting in HCC progression.CONCLUSION FLOT1 recruits and inhibits mechanistic target of rapamycin complex 1/2,causing dephosphorylation and TFE3 nuclear translocation,thereby activating the Golgi stress response and further promoting the proliferation,migration,and invasion capabilities of HCC cells.These results underscore the potential of FLOT1 as a promising therapeutic target for HCC.展开更多
Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandin...Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive.Here,we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell(MSC)function and regeneration.Interestingly,replenishment of cell aggregates-derived extracellular vesicles(CA-EVs)rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5.Importantly,in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice,suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration.Collectively,our findings provide insights into Golgi regulation in stem cell senescence and bone aging,which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.展开更多
In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)pro...In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.展开更多
Objectives:Triple-negative breast cancer(TNBC)presents a major treatment challenge due to its aggressive behavior.The dysfunction of the Golgi apparatus(GA)contributes to the development of various cancers.This study ...Objectives:Triple-negative breast cancer(TNBC)presents a major treatment challenge due to its aggressive behavior.The dysfunction of the Golgi apparatus(GA)contributes to the development of various cancers.This study aimed to utilize GA-related genes(GARGs)to forecast the prognosis and immune profile of TNBC.Methods:The data were downloaded from The Cancer Genome Atlas(TCGA)database,including 175 TNBC and 99 healthy samples.The differentially expressed GARGs(DEGARGs)were analyzed using the TCGA biolinks package.The patients with TNBC were classified into two clusters utilizing the ConsensusClusterPlus package according to prognosis-related DEGARGs,followed by comparing the differences in prognosis and immune infiltration between the two clusters.Next,LASSO and stepwise Cox regression were applied to establish a GARGs signature to forecast the TNBC prognosis.The association of the GARGs signature with immune infiltrates and drug sensitivity was further explored.Results:In total,430 DEGARGs were identified between TNBC and healthy samples,among which 20 were related to TNBC prognosis.Two GARG-related molecular clusters associated with different survival times and immune heterogeneity were identified.A risk model for TNBC was established based on six GARGs,and the high-risk(HR)group exhibited a poor prognosis.The HR group demonstrated a distinctly high M2 macrophage infiltration and low M1 macrophage infiltration,which contributed to an immunosuppressive tumor microenvironment and thus led to poor prognosis of the HR group.Immune dysfunction scores and programmed cell death ligand 1(PD-L1)expression were substantially elevated in the HR group.The HR group showed increased sensitivity to anticancer drugs,such as cisplatin.Conclusion:Our findings suggest that GARGs are involved in the pathogenesis of TNBC and provide new insights into prognostic prediction.The identified clusters and GARGs signatures have the potential to guide individualized therapy.展开更多
The histological basis for acute osteocyte mechanosensitivity remains uncertain. A novel bone cell model of mechanotransduction and inorganic trafficking may be the powerful, silt-burrowing protozoan Spirostomum ambig...The histological basis for acute osteocyte mechanosensitivity remains uncertain. A novel bone cell model of mechanotransduction and inorganic trafficking may be the powerful, silt-burrowing protozoan Spirostomum ambiguum which when being physically challenged fabricates within vesicles populations of bone-like calcium phosphate microspheres, about 1 μm in diameter. These not only attribute considerable compression-resilience but also resemble the Golgi-directed mineral assemblies we recently reported in osteocytes. Advantageously, calcification in the protozoan (confirmed by ultramicroscopy with EDX elemental microanalysis) enabled Golgi comparison under overt, natural phases of both high (i.e. silt-tunnelling) and low (i.e free-swimming) stress. Established hard-tissue microscopy techniques previously positive in bone cells included quantitative fluorescent tetracycline labelling for bone salt together with the same metazoan Golgi body marker (Green Fluorescent Protein-tagged mannosidase II construct). Organellar modulation was monitored by transfection of live organisms in situ (some post-stained with red nuclear fluorochrome TOPRO-3). Results showed that GFP-tagged Golgi fluorescence increased from swimmers (mean 74.5 ± SD 6.7 AU) to burrowers (mean 104.6 ± SD 2.7;p < 0.0001) synchronous with juxtanuclear tetracycline-labelled mineral fluorescence (swimmers, mean 89.7 ± SD 3.3 AU;burrowers, mean 138.0 ± SD 4.0;p < 0.0001). Intracellular dense microspheres, single or bridged, were harvested as pellets rich in Ca, P (Ca:P 0.98) and Si, their polarised alignment moving from transaxial in swimmers to axial in burrowers. It was concluded that Golgi-directed mineral fabrication in the large, accessible, silt-enclosed ciliate resembles that in the smaller, less-accessible bone cell and may be a conserved early mechanobiological intracellular development predicating force translation into compression-resistant mineral fabrication in loaded segments of the osteocyte syncitium.展开更多
Golgi apparatus,together with endoplasmic reticula,vacuoles and plasma membrane,constitutes the endoplasmic system of plant cells.It plays an important role in the secretion pathway of eukaryotic cells and is responsi...Golgi apparatus,together with endoplasmic reticula,vacuoles and plasma membrane,constitutes the endoplasmic system of plant cells.It plays an important role in the secretion pathway of eukaryotic cells and is responsible for various intracellular events,such as protein classification,protein modification and glycosylation.At present,much less is known about plant Golgi proteins.The research on its function is still insufficient.In order to provide a comprehensive research background and research ideas for related researchers,this paper systematically and comprehensively evaluated the structure of plant endoplasmic system,the common endoplasmic reticulum-Golgi transport pathway in plant cells,various possible transport models between endoplasmic reticula and Golgi bodies,Golgi-associated specific proteins and functions,and Golgi biogenesis pathway.The latest research progress in this field was reviewed and analyzed in detail.This paper will provide an important reference for related researchers to carry out the research of plant Golgi.展开更多
Blood samples were harvested from the antecubital vein of 20 fasting patients with acute cerebral infarction at 1, 7 and 15 days after onset to prepare blood platelet suspension. Fasting antecubital vein blood was col...Blood samples were harvested from the antecubital vein of 20 fasting patients with acute cerebral infarction at 1, 7 and 15 days after onset to prepare blood platelet suspension. Fasting antecubital vein blood was collected from an additional 20 normal adults as controls. Under transmission elec- tron microscope, platelet Golgi tubules and vesicles became significantly thickened, enlarged, and irregular after acute cerebral infarction. Alpha granules in platelets significantly reduced in number, especially 1 day after cerebral infarction. Under immunoelectron microscopy, a few alpha granules aggregated around Golgi tubules and vesicles after infarction. These results suggested that platelet Golgi apparatus displayed significant morphological changes, which were possibly associated with enhanced synthetic and secretory functions of activated platelets after acute cerebral infarction. This study used Golgi apparatus blocking agent Brefeldin A to block Golgi apparatus in an aim to study the effects of Golgi apparatus on CD40L expression on the surface of activated platelets. Flow cytometry revealed that CD40L expression on activated platelet surfaces decreased significantly when Golgi apparatus was blocked, which indicated that Golgi apparatus participated in the syn- thesis and transport of CD40L to the platelet surface.展开更多
AIM: To investigate the effect of Golgi phosphorylation protein 3(GOLPH3) expression on cell apoptosis, angiogenesis and prognosis in colorectal cancer(CRC). METHODS: The expression of GOLPH3 in CRC tissues and normal...AIM: To investigate the effect of Golgi phosphorylation protein 3(GOLPH3) expression on cell apoptosis, angiogenesis and prognosis in colorectal cancer(CRC). METHODS: The expression of GOLPH3 in CRC tissues and normal colorectal mucosae was determined by immunohistochemistry in 62 patients. In addition, immunohistochemistry was also carried out to detect the expression of vascular endothelial growth factor(VEGF), CD34 and microvessel density(MVD). Terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling assay was used to determine the apoptotic index(AI). The Kaplan-Meier method was used to analyze the relationship between GOLPH3 expression and survival in another 123 CRC cases.RESULTS: Compared with normal colorectal mucosae, a notably higher level of GOLPH3 protein expression was identified in CRC tissues(53.2% vs 24.2%, P < 0.05). Positive GOLPH3 expression was significantly associated with tumor invasion depth, TNM stage, and lymph node metastasis(P = 0.001; P = 0.020; P = 0.020; P < 0.05, respectively), but not with tumor length, tumor site, and age(P = 0.363; P = 0.819; P = 0.599; P > 0.05, respectively). VEGF expression and MVD in GOLPH3-positive CRC was significantly higher than in GOLPH3-negative CRC(VEGF: 69.7% vs 31.0%; MVD: 21.45 ± 9.39 vs 14.24 ± 8.97; P < 0.05).GOLPH3 expression was negatively correlated with AI in CRC as shown by Spearman correlation analysis(r =-0.320, P < 0.05). The 5-year survival rate in GOLPH3-negative CRC(69.4%) was significantly higher than in GOLPH3-positive CRC(48.6%)(log-rank test, P < 0.05).CONCLUSION: High expression of GOLPH3 is found in CRC tissues. GOLPH3 expression may be a novel prognostic marker for CRC patients.展开更多
Maintenance of the Golgi apparatus （GA） structure and function depends on Golgi matrix proteins. The posttranslational modification of Golgi proteins such as phosphorylation of members of the golgin and GRASP famili...Maintenance of the Golgi apparatus （GA） structure and function depends on Golgi matrix proteins. The posttranslational modification of Golgi proteins such as phosphorylation of members of the golgin and GRASP families is important for determining Golgi architecture. Some Golgi proteins including golgin-84 are also known to be methylated, but the function of golgin methylation remains unclear. Here, we show that the protein arginine methyltransferase 5 （PRMT5） localizes to the GA and forms complexes with several components involved in GA ribbon formation and vesicle tethering. PRMT5 interacts with the golgin GM130, and depletion of PRMT5 causes defects in Golgi ribbon formation. Furthermore, PRMT5 methylates N-terminal arginines in GM130, and such arginine methylation appears critical for GA ribbon formation. Our findings reveal a molecular mechanism by which PRMT5-dependent arginine methylation of GM130 controls the maintenance of GA architecture.展开更多
BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally de...BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.展开更多
基金Supported by the National Natural Science Foundation of China,No.82203806the General Hospital of Western Theater Command Project Funding,No.2024-YGJC-B10.
文摘BACKGROUND It is critical to explore effective therapeutic targets for improving the survival rate of patients with hepatocellular carcinoma(HCC).Although many studies have focused on flotillin-1(FLOT1)as a lipid raft-associated protein that regulates the activation of some proteins or kinases to promote tumor cell survival and proliferation,few studies have explored the regulation of Golgi apparatus function.AIM To investigate the molecular mechanism through which FLOT1 activates the Golgi stress response downstream of transcription factor E3(TFE3),thereby promoting the progression of HCC.METHODS FLOT1 expression in HCC tissue,HCC cell lines,and nude mouse tumor models was assessed.The impact of FLOT1 silencing or its overexpression on the proliferation of HCC cells was studied.CCK-8,flow cytometry,and transwell assays were used to assess the proliferation,cell cycle,migration,and invasion abilities of HCC cells.A dual-luciferase reporter assay was used to study the effect of FLOT1 on the transcriptional activity of the downstream Golgi apparatus stress element promoter of TFE3.Western blotting,co-immunoprecipitation,and immunofluorescence staining were employed to detect relevant proteins.RESULTS High FLOT1 expression was correlated with a poor prognosis in patients with HCC.The knockdown of FLOT1 suppressed the proliferation,migration,and invasion of HCC cells and promoted their apoptosis.Xenograft assays revealed that FLOT1 knockdown inhibited HCC tumorigenesis in vivo.Mechanistically,FLOT1 inhibited the expression of mechanistic target of rapamycin complex 1/2 proteins through ubiquitination and downstream effector p-S6 kinase-T389,leading to the dephosphorylation and nuclear translocation of TFE3 and promotion of Golgi stress-mediated responses,ultimately resulting in HCC progression.CONCLUSION FLOT1 recruits and inhibits mechanistic target of rapamycin complex 1/2,causing dephosphorylation and TFE3 nuclear translocation,thereby activating the Golgi stress response and further promoting the proliferation,migration,and invasion capabilities of HCC cells.These results underscore the potential of FLOT1 as a promising therapeutic target for HCC.
基金supported by grants from the National Natural Science Foundation of China(81930025,82201013,82371020,82370949,82100992)the Young Science and Technology Rising Star Project of Shaanxi Province(2023KJXX-027)the China Postdoctoral Science Foundation(BX20230485).
文摘Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive.Here,we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell(MSC)function and regeneration.Interestingly,replenishment of cell aggregates-derived extracellular vesicles(CA-EVs)rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5.Importantly,in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice,suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration.Collectively,our findings provide insights into Golgi regulation in stem cell senescence and bone aging,which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.
基金Supported by Italian Association for Cancer Research(AIRC),No.21956Italian Ministry of Health-5×1000 funds 2023.
文摘In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.
文摘Objectives:Triple-negative breast cancer(TNBC)presents a major treatment challenge due to its aggressive behavior.The dysfunction of the Golgi apparatus(GA)contributes to the development of various cancers.This study aimed to utilize GA-related genes(GARGs)to forecast the prognosis and immune profile of TNBC.Methods:The data were downloaded from The Cancer Genome Atlas(TCGA)database,including 175 TNBC and 99 healthy samples.The differentially expressed GARGs(DEGARGs)were analyzed using the TCGA biolinks package.The patients with TNBC were classified into two clusters utilizing the ConsensusClusterPlus package according to prognosis-related DEGARGs,followed by comparing the differences in prognosis and immune infiltration between the two clusters.Next,LASSO and stepwise Cox regression were applied to establish a GARGs signature to forecast the TNBC prognosis.The association of the GARGs signature with immune infiltrates and drug sensitivity was further explored.Results:In total,430 DEGARGs were identified between TNBC and healthy samples,among which 20 were related to TNBC prognosis.Two GARG-related molecular clusters associated with different survival times and immune heterogeneity were identified.A risk model for TNBC was established based on six GARGs,and the high-risk(HR)group exhibited a poor prognosis.The HR group demonstrated a distinctly high M2 macrophage infiltration and low M1 macrophage infiltration,which contributed to an immunosuppressive tumor microenvironment and thus led to poor prognosis of the HR group.Immune dysfunction scores and programmed cell death ligand 1(PD-L1)expression were substantially elevated in the HR group.The HR group showed increased sensitivity to anticancer drugs,such as cisplatin.Conclusion:Our findings suggest that GARGs are involved in the pathogenesis of TNBC and provide new insights into prognostic prediction.The identified clusters and GARGs signatures have the potential to guide individualized therapy.
文摘The histological basis for acute osteocyte mechanosensitivity remains uncertain. A novel bone cell model of mechanotransduction and inorganic trafficking may be the powerful, silt-burrowing protozoan Spirostomum ambiguum which when being physically challenged fabricates within vesicles populations of bone-like calcium phosphate microspheres, about 1 μm in diameter. These not only attribute considerable compression-resilience but also resemble the Golgi-directed mineral assemblies we recently reported in osteocytes. Advantageously, calcification in the protozoan (confirmed by ultramicroscopy with EDX elemental microanalysis) enabled Golgi comparison under overt, natural phases of both high (i.e. silt-tunnelling) and low (i.e free-swimming) stress. Established hard-tissue microscopy techniques previously positive in bone cells included quantitative fluorescent tetracycline labelling for bone salt together with the same metazoan Golgi body marker (Green Fluorescent Protein-tagged mannosidase II construct). Organellar modulation was monitored by transfection of live organisms in situ (some post-stained with red nuclear fluorochrome TOPRO-3). Results showed that GFP-tagged Golgi fluorescence increased from swimmers (mean 74.5 ± SD 6.7 AU) to burrowers (mean 104.6 ± SD 2.7;p < 0.0001) synchronous with juxtanuclear tetracycline-labelled mineral fluorescence (swimmers, mean 89.7 ± SD 3.3 AU;burrowers, mean 138.0 ± SD 4.0;p < 0.0001). Intracellular dense microspheres, single or bridged, were harvested as pellets rich in Ca, P (Ca:P 0.98) and Si, their polarised alignment moving from transaxial in swimmers to axial in burrowers. It was concluded that Golgi-directed mineral fabrication in the large, accessible, silt-enclosed ciliate resembles that in the smaller, less-accessible bone cell and may be a conserved early mechanobiological intracellular development predicating force translation into compression-resistant mineral fabrication in loaded segments of the osteocyte syncitium.
基金Special Fund for the Research Team of Ecological Restoration and Governance Innovation of the Jinsha River Dry and Hot Valley(035200179)2020 Doctoral Research Startup Fund of Panzhihua University(035200254)。
文摘Golgi apparatus,together with endoplasmic reticula,vacuoles and plasma membrane,constitutes the endoplasmic system of plant cells.It plays an important role in the secretion pathway of eukaryotic cells and is responsible for various intracellular events,such as protein classification,protein modification and glycosylation.At present,much less is known about plant Golgi proteins.The research on its function is still insufficient.In order to provide a comprehensive research background and research ideas for related researchers,this paper systematically and comprehensively evaluated the structure of plant endoplasmic system,the common endoplasmic reticulum-Golgi transport pathway in plant cells,various possible transport models between endoplasmic reticula and Golgi bodies,Golgi-associated specific proteins and functions,and Golgi biogenesis pathway.The latest research progress in this field was reviewed and analyzed in detail.This paper will provide an important reference for related researchers to carry out the research of plant Golgi.
基金supported by grants from the National Natural Science Foundation of China, No.81171239/H0914Frontier Research Key Project,Central South University in China (2010-2011), No.2177-721500065the Education Expenditure of Hunan Provincial Finance Department in China, No.2010163
文摘Blood samples were harvested from the antecubital vein of 20 fasting patients with acute cerebral infarction at 1, 7 and 15 days after onset to prepare blood platelet suspension. Fasting antecubital vein blood was collected from an additional 20 normal adults as controls. Under transmission elec- tron microscope, platelet Golgi tubules and vesicles became significantly thickened, enlarged, and irregular after acute cerebral infarction. Alpha granules in platelets significantly reduced in number, especially 1 day after cerebral infarction. Under immunoelectron microscopy, a few alpha granules aggregated around Golgi tubules and vesicles after infarction. These results suggested that platelet Golgi apparatus displayed significant morphological changes, which were possibly associated with enhanced synthetic and secretory functions of activated platelets after acute cerebral infarction. This study used Golgi apparatus blocking agent Brefeldin A to block Golgi apparatus in an aim to study the effects of Golgi apparatus on CD40L expression on the surface of activated platelets. Flow cytometry revealed that CD40L expression on activated platelet surfaces decreased significantly when Golgi apparatus was blocked, which indicated that Golgi apparatus participated in the syn- thesis and transport of CD40L to the platelet surface.
基金Supported by The Scientific Research Fund from the Science and Technology Bureau of QuanzhouChinaNo.2010Z33
文摘AIM: To investigate the effect of Golgi phosphorylation protein 3(GOLPH3) expression on cell apoptosis, angiogenesis and prognosis in colorectal cancer(CRC). METHODS: The expression of GOLPH3 in CRC tissues and normal colorectal mucosae was determined by immunohistochemistry in 62 patients. In addition, immunohistochemistry was also carried out to detect the expression of vascular endothelial growth factor(VEGF), CD34 and microvessel density(MVD). Terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling assay was used to determine the apoptotic index(AI). The Kaplan-Meier method was used to analyze the relationship between GOLPH3 expression and survival in another 123 CRC cases.RESULTS: Compared with normal colorectal mucosae, a notably higher level of GOLPH3 protein expression was identified in CRC tissues(53.2% vs 24.2%, P < 0.05). Positive GOLPH3 expression was significantly associated with tumor invasion depth, TNM stage, and lymph node metastasis(P = 0.001; P = 0.020; P = 0.020; P < 0.05, respectively), but not with tumor length, tumor site, and age(P = 0.363; P = 0.819; P = 0.599; P > 0.05, respectively). VEGF expression and MVD in GOLPH3-positive CRC was significantly higher than in GOLPH3-negative CRC(VEGF: 69.7% vs 31.0%; MVD: 21.45 ± 9.39 vs 14.24 ± 8.97; P < 0.05).GOLPH3 expression was negatively correlated with AI in CRC as shown by Spearman correlation analysis(r =-0.320, P < 0.05). The 5-year survival rate in GOLPH3-negative CRC(69.4%) was significantly higher than in GOLPH3-positive CRC(48.6%)(log-rank test, P < 0.05).CONCLUSION: High expression of GOLPH3 is found in CRC tissues. GOLPH3 expression may be a novel prognostic marker for CRC patients.
文摘Maintenance of the Golgi apparatus （GA） structure and function depends on Golgi matrix proteins. The posttranslational modification of Golgi proteins such as phosphorylation of members of the golgin and GRASP families is important for determining Golgi architecture. Some Golgi proteins including golgin-84 are also known to be methylated, but the function of golgin methylation remains unclear. Here, we show that the protein arginine methyltransferase 5 （PRMT5） localizes to the GA and forms complexes with several components involved in GA ribbon formation and vesicle tethering. PRMT5 interacts with the golgin GM130, and depletion of PRMT5 causes defects in Golgi ribbon formation. Furthermore, PRMT5 methylates N-terminal arginines in GM130, and such arginine methylation appears critical for GA ribbon formation. Our findings reveal a molecular mechanism by which PRMT5-dependent arginine methylation of GM130 controls the maintenance of GA architecture.
文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.
