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  1. Article ; Online: Inhibition of spastin impairs motor function recovery after spinal cord injury.

    Yang, Jie / Zhang, Yunlong / Cai, Zhenbin / Zou, Jianyu / Li, Shaojin / Miao, Guiqiang / Lin, Hongsheng / Zhao, Xiaodong / Tan, Minghui

    Brain research bulletin

    2023  Volume 205, Page(s) 110806

    Abstract: Promoting axonal regeneration is an effective strategy for recovery from traumatic spinal cord injury (SCI). Spastin, a microtubule-severing protein, modulates axonal outgrowth and branch formation by regulating microtubule dynamics. However, the exact ... ...

    Abstract Promoting axonal regeneration is an effective strategy for recovery from traumatic spinal cord injury (SCI). Spastin, a microtubule-severing protein, modulates axonal outgrowth and branch formation by regulating microtubule dynamics. However, the exact role of spastin during recovery from SCI remains unknown. Therefore, we utilized a hemisection injury model of the mouse spinal cord and explored the effect of spastin using a spastin inhibitor, spastazoline. Results showed that spastazoline significantly suppressed the microtubule-severing activity of spastin in COS-7 cells and inhibited the promoting effect of spastin on neurite outgrowth in primarily cultured hippocampal neurons. The protein expression level of spastin was significantly upregulated in the injured spinal cord. Injured mice showed impaired motor functions, which included increased toe-off angle and foot fault steps and decreased stride length and Basso mouse scale score. Notably, these motor function impairments were aggravated by the application of spastazoline. Inhibition of spastin exacerbated neurogenesis impairment, as demonstrated by neuronal nuclei antigen staining, the inflammatory response, as shown by Iba-1 and GFAP staining, and axonal regeneration impairment, as shown by 5-hydroxytryptamine staining. Furthermore, mass spectrometry analysis revealed that the inhibition of spastin resulted in numerous dysregulated differentially expressed proteins that were closely associated with vesicle organization and transport. Taken together, our data suggest that spastin is critical for recovery from SCI and may be a potential target for the treatment of SCI.
    MeSH term(s) Animals ; Mice ; Neurons/metabolism ; Recovery of Function/physiology ; Spastin/antagonists & inhibitors ; Spastin/metabolism ; Spinal Cord/metabolism ; Spinal Cord Injuries/drug therapy ; Spinal Cord Injuries/metabolism
    Chemical Substances Spastin (EC 3.6.4.3)
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 197620-5
    ISSN 1873-2747 ; 0361-9230
    ISSN (online) 1873-2747
    ISSN 0361-9230
    DOI 10.1016/j.brainresbull.2023.110806
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development of a predictive nomogram for 28-day mortality risk in non-traumatic or post-traumatic subarachnoid hemorrhage patients.

    Miao, Guiqiang / Cai, Zhenbin / He, Xin / Yang, Jie / Zhang, Yunlong / Ma, Ao / Zhao, Xiaodong / Tan, Minghui

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

    2023  Volume 45, Issue 5, Page(s) 2149–2163

    Abstract: Objective: Subarachnoid hemorrhage (SAH) is associated with high rates of mortality and permanent disability. At present, there are few definite clinical tools to predict prognosis in SAH patients. The current study aims to develop and assess a ... ...

    Abstract Objective: Subarachnoid hemorrhage (SAH) is associated with high rates of mortality and permanent disability. At present, there are few definite clinical tools to predict prognosis in SAH patients. The current study aims to develop and assess a predictive nomogram model for estimating the 28-day mortality risk in both non-traumatic or post-traumatic SAH patients.
    Methods: The MIMIC-III database was searched to select patients with SAH based on ICD-9 codes. Patients were separated into non-traumatic and post-traumatic SAH groups. Using LASSO regression analysis, we identified independent risk factors associated with 28-day mortality and incorporated them into nomogram models. The performance of each nomogram was assessed by calculating various metrics, including the area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA).
    Results: The study included 999 patients with SAH, with 631 in the non-traumatic group and 368 in the post-traumatic group. Logistic regression analysis revealed critical independent risk factors for 28-day mortality in non-traumatic SAH patients, including gender, age, glucose, platelet, sodium, BUN, WBC, PTT, urine output, SpO
    Conclusion: The study identified independent risk factors associated with the 28-day mortality risk and developed predictive nomogram models for both non-traumatic and post-traumatic SAH patients. The nomogram holds promise in guiding prognosis improvement strategies for patients with SAH.
    MeSH term(s) Humans ; Subarachnoid Hemorrhage, Traumatic ; Nomograms ; Subarachnoid Hemorrhage/complications ; Area Under Curve ; Glucose ; Prognosis ; Retrospective Studies
    Chemical Substances Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-11-23
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2016546-8
    ISSN 1590-3478 ; 1590-1874
    ISSN (online) 1590-3478
    ISSN 1590-1874
    DOI 10.1007/s10072-023-07199-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Venous thromboembolism prophylaxis and mortality in patients with spinal fractures in ICUs.

    Li, Shaojin / Zhang, Luming / Yin, Haiyan / Zhang, Guowei / Tan, Minghui / Cai, Zhenbin / Huang, Tao / Lin, Hongsheng / Lyu, Jun

    Nursing in critical care

    2023  Volume 29, Issue 3, Page(s) 564–572

    Abstract: Background: Spinal fracture is a common traumatic condition in orthopaedics, accounting for 5%-6% of total body fractures, and is a high-risk factor for venous thromboembolism (VTE), which seriously affects patient prognosis.: Aim: The aim of this ... ...

    Abstract Background: Spinal fracture is a common traumatic condition in orthopaedics, accounting for 5%-6% of total body fractures, and is a high-risk factor for venous thromboembolism (VTE), which seriously affects patient prognosis.
    Aim: The aim of this study was to determine the impact of VTE prophylaxis on the prognosis of patients with spinal fractures in intensive care units (ICUs) and to provide a scientific basis for clinical treatment and nursing.
    Design: A retrospective study of patients with spinal fractures from the multicenter eICU Collaborative Research Database.
    Method: The outcomes of this study were ICU mortality and in-hospital mortality. Patients were divided into the VTE prophylaxis (VP) and no VTE prophylaxis (NVP) groups according to whether they had undergone VTE prophylaxis during their ICU admission. The association between groups and outcomes were analysed using Kaplan-Meier (KM) survival curve, log-rank test and the Cox proportional-hazards regression model.
    Results: This study included 1146 patients with spinal fractures: 330 in the VP group and 816 in the NVP group. KM survival curves and log-rank tests revealed that both ICU and in-hospital survival probabilities in the VP group were significantly higher than in the NVP group. After the Cox model was adjusted for all covariates, the hazard ratio for ICU mortality in the VP group was 0.38 (0.19-0.75); the corresponding value for in-hospital mortality in the VP group was 0.38 (0.21-0.68).
    Conclusions: VTE prophylaxis is associated with reduced ICU and in-hospital mortality in patients with spinal fractures in ICUs. More research is necessary to further define specific strategies and optimal timing for VTE prophylaxis.
    Relevance to clinical practice: This study provides the basis that VTE prophylaxis may be associated with improved prognosis in patients with spinal fractures in ICUs. In clinical practice, an appropriate modality should be selected for VTE prophylaxis in such patients.
    MeSH term(s) Humans ; Venous Thromboembolism/prevention & control ; Male ; Female ; Retrospective Studies ; Intensive Care Units ; Hospital Mortality ; Middle Aged ; Spinal Fractures/mortality ; Aged ; Risk Factors ; Anticoagulants/therapeutic use ; Prognosis ; Proportional Hazards Models
    Chemical Substances Anticoagulants
    Language English
    Publishing date 2023-04-11
    Publishing country England
    Document type Journal Article ; Multicenter Study
    ZDB-ID 2011956-2
    ISSN 1478-5153 ; 1362-1017
    ISSN (online) 1478-5153
    ISSN 1362-1017
    DOI 10.1111/nicc.12915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Association of serum mannose-binding lectin, anti-phospholipase A2 receptor antibody and renal outcomes in idiopathic membranous nephropathy and atypical membranous nephropathy: a single center retrospective cohort study.

    Zhao, Yuchao / Cai, Meishun / Jiang, Zhenbin / Dong, Bao / Yan, Yu / Wang, Yina / Zuo, Li

    Renal failure

    2022  Volume 44, Issue 1, Page(s) 428–433

    Abstract: Objectives: Idiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a 'full-house' on immunofluorescent examination, that is IgG, IgA, ... ...

    Abstract Objectives: Idiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a 'full-house' on immunofluorescent examination, that is IgG, IgA, IgM, C3, C1q positive, but without clinical evidence of a secondary cause. Phospholipase A2 receptor (PLA2R) was the major target antigens in iMN patients. Activation of the mannose-binding lectin (MBL) pathway plays a vital role in the development of MN. Our objective was to investigate the role of PLA2R and MBL in the pathogenesis of iMN and aMN.
    Methods: We conducted a retrospective observational study using propensity score matching by age, gender, and eGFR. All clinical, laboratory data, and follow-up data of the patients were collected. Serum levels of anti-PLA2R antibodies and MBL were tested.
    Results: Finally, 30 iMN patients and 30 aMN patients were included, and 20 healthy controls were retrospectively collected in this study. The 24 h proteinuria level was higher and serum albumin was lower in anti-PLA2R (+) patients than in anti-PLA2R (-) patients in both iMN and aMN groups. In aMN patients, MBL levels were significantly higher in anti-PLA2R (+) patients than in anti-PLA2R (-) patients (
    Conclusions: The complement lectin pathway has an association with the development of MN, especially in patients with positive anti-PLA2R antibodies. Serum MBL cannot differentiate between the two diseases. Serum MBL levels are not associated with clinical manifestations, nor with prognosis.
    MeSH term(s) Adult ; Aged ; Autoantibodies/blood ; Female ; Glomerulonephritis, Membranous/blood ; Glomerulonephritis, Membranous/immunology ; Humans ; Kidney/metabolism ; Kidney/pathology ; Logistic Models ; Male ; Mannose-Binding Lectin/blood ; Middle Aged ; Propensity Score ; Receptors, Phospholipase A2/genetics ; Receptors, Phospholipase A2/immunology ; Retrospective Studies
    Chemical Substances Autoantibodies ; Mannose-Binding Lectin ; PLA2R1 protein, human ; Receptors, Phospholipase A2
    Language English
    Publishing date 2022-03-01
    Publishing country England
    Document type Journal Article ; Observational Study
    ZDB-ID 632949-4
    ISSN 1525-6049 ; 0886-022X
    ISSN (online) 1525-6049
    ISSN 0886-022X
    DOI 10.1080/0886022X.2022.2048016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Rab3A interacts with spastin to regulate neurite outgrowth in hippocampal neurons.

    Yang, Yuhao / Yang, Jie / Liang, Yaozhong / Zhang, Guowei / Cai, Zhenbin / Zhang, Yunlong / Lin, Hongsheng / Tan, Minghui

    Biochemical and biophysical research communications

    2022  Volume 643, Page(s) 77–87

    Abstract: Investigating novel mechanisms of neurite outgrowth via cytoskeleton is critical for developing therapeutic strategies against neural disorders. Rab3A is a vesicle-related protein distributed throughout the nervous system, but the detailed mechanism ... ...

    Abstract Investigating novel mechanisms of neurite outgrowth via cytoskeleton is critical for developing therapeutic strategies against neural disorders. Rab3A is a vesicle-related protein distributed throughout the nervous system, but the detailed mechanism related to cytoskeleton remains largely unknown. Our previous reports show that spastin serves microtubule to regulate neurite outgrowth. Here, we asked whether Rab3A could function via modulating spastin during neuronal development. The results revealed that Rab3A colocalized with spastin in cultured hippocampal neurons. Immunoprecipitation assays showed that Rab3A physically interacted with spastin in rat brain lysates. Rab3A overexpression significantly induced spastin degradation; this effect was reversed by leupeptin- or MG-132- administration, suggesting the lysosomal and ubiquitin-mediated degradation system. Immunofluorescence staining further confirmed that Rab3A and spastin immune-colocalized with the lysosome marker lysotracker. In COS7 cells, Rab3A overexpression significantly downregulated spastin expression and abolished the spastin-mediated microtubule severing. Furthermore, overexpression inhibited while genetic knockdown of Rab3A promoted neurite outgrowth. However, this inhibitory effect on neurite outgrowth in hippocampal neurons could be reversed via co-transfection of spastin, indicating that Rab3A functions via its interaction protein spastin. In general, our data identify an interaction between Rab3A and spastin, and this interaction affects the protein stability of spastin and eliminates its microtubule severing function, thereby modulating neurite outgrowth.
    MeSH term(s) Animals ; Rats ; Adenosine Triphosphatases/metabolism ; Neurites/metabolism ; Neuronal Outgrowth ; Neurons/metabolism ; rab3A GTP-Binding Protein ; Spastic Paraplegia, Hereditary/genetics ; Spastic Paraplegia, Hereditary/metabolism ; Spastin/metabolism ; Spastin/pharmacology
    Chemical Substances Adenosine Triphosphatases (EC 3.6.1.-) ; rab3A GTP-Binding Protein (EC 3.6.5.2) ; Rab3a protein, rat ; Spastin (EC 3.6.4.3) ; Spast protein, rat (EC 5.6.1.1)
    Language English
    Publishing date 2022-12-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.12.066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Development and validation of a nomogram to predict the 30-day mortality risk of patients with intracerebral hemorrhage.

    Zou, Jianyu / Chen, Huihuang / Liu, Cuiqing / Cai, Zhenbin / Yang, Jie / Zhang, Yunlong / Li, Shaojin / Lin, Hongsheng / Tan, Minghui

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 942100

    Abstract: Background: Intracerebral hemorrhage (ICH) is a stroke syndrome with an unfavorable prognosis. Currently, there is no comprehensive clinical indicator for mortality prediction of ICH patients. The purpose of our study was to construct and evaluate a ... ...

    Abstract Background: Intracerebral hemorrhage (ICH) is a stroke syndrome with an unfavorable prognosis. Currently, there is no comprehensive clinical indicator for mortality prediction of ICH patients. The purpose of our study was to construct and evaluate a nomogram for predicting the 30-day mortality risk of ICH patients.
    Methods: ICH patients were extracted from the MIMIC-III database according to the ICD-9 code and randomly divided into training and verification cohorts. The least absolute shrinkage and selection operator (LASSO) method and multivariate logistic regression were applied to determine independent risk factors. These risk factors were used to construct a nomogram model for predicting the 30-day mortality risk of ICH patients. The nomogram was verified by the area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA).
    Results: A total of 890 ICH patients were included in the study. Logistic regression analysis revealed that age (OR = 1.05,
    Conclusion: This study identified independent risk factors for 30-day mortality of ICH patients and constructed a predictive nomogram model, which may help to improve the prognosis of ICH patients.
    Language English
    Publishing date 2022-08-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.942100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: SUMOylation of microtubule-cleaving enzyme KATNA1 promotes microtubule severing and neurite outgrowth.

    Li, Shaojin / Liang, Yaozhong / Zou, Jianyu / Cai, Zhenbin / Yang, Hua / Yang, Jie / Zhang, Yunlong / Lin, Hongsheng / Zhang, Guowei / Tan, Minghui

    The Journal of biological chemistry

    2022  Volume 298, Issue 9, Page(s) 102292

    Abstract: Katanin p60 ATPase-containing subunit A1 (KATNA1) is a microtubule-cleaving enzyme that regulates the development of neural protrusions through cytoskeletal rearrangements. However, the mechanism underlying the linkage of the small ubiquitin-like ... ...

    Abstract Katanin p60 ATPase-containing subunit A1 (KATNA1) is a microtubule-cleaving enzyme that regulates the development of neural protrusions through cytoskeletal rearrangements. However, the mechanism underlying the linkage of the small ubiquitin-like modifier (SUMO) protein to KATNA1 and how this modification regulates the development of neural protrusions is unclear. Here we discovered, using mass spectrometry analysis, that SUMO-conjugating enzyme UBC9, an enzyme necessary for the SUMOylation process, was present in the KATNA1 interactome. Moreover, GST-pull down and co-immunoprecipitation assays confirmed that KATNA1 and SUMO interact. We further demonstrated using immunofluorescence experiments that KATNA1 and the SUMO2 isoform colocalized in hippocampal neurites. We also performed a bioinformatics analysis of KATNA1 protein sequences to identify three potentially conserved SUMOylation sites (K77, K157, and K330) among vertebrates. Mutation of K330, but not K77 or K157, abolished KATNA1-induced microtubule severing and decreased the level of binding observed for KATNA1 and SUMO2. Cotransfection of SUMO2 and wildtype KATNA1 in COS7 cells increased microtubule severing, whereas no effect was observed after cotransfection with the K330R KATNA1 mutant. Furthermore, in cultured hippocampal neurons, overexpression of wildtype KATNA1 significantly promoted neurite outgrowth, whereas the K330R mutant eliminated this effect. Taken together, our results demonstrate that the K330 site in KATNA1 is modified by SUMOylation and SUMOylation of KATNA1 promotes microtubule dynamics and hippocampal neurite outgrowth.
    MeSH term(s) Adenosine Triphosphatases/metabolism ; Animals ; COS Cells ; Chlorocebus aethiops ; HEK293 Cells ; Humans ; Katanin/genetics ; Katanin/metabolism ; Microtubules/enzymology ; Microtubules/genetics ; Neuronal Outgrowth ; Sumoylation ; Ubiquitin/metabolism ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Conjugating Enzymes/metabolism
    Chemical Substances Ubiquitin ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Adenosine Triphosphatases (EC 3.6.1.-) ; KATNA1 protein, human (EC 5.6.1.1) ; Katanin (EC 5.6.1.1) ; ubiquitin-conjugating enzyme UBC9 (EC 6.3.2.-)
    Language English
    Publishing date 2022-07-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2022.102292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: PlexinA3 Interacts with CRMP2 to Mediate Sema3A Signalling During Dendritic Growth in Cultured Cerebellar Granule Neurons.

    Jiang, Tao / Zhang, Guowei / Liang, Yaozhong / Cai, Zhenbin / Liang, Zhi / Lin, Hongsheng / Tan, Minghui

    Neuroscience

    2020  Volume 434, Page(s) 83–92

    Abstract: Plexin family proteins mediate semaphorin signalling during dendritic arbour development. However, the role of PlexinA3 in the growth of dendrites of cultured cerebellar granule neurons (CGNs) is not known. We found that PlexinA3 colocalizes with CRMP2 ( ... ...

    Abstract Plexin family proteins mediate semaphorin signalling during dendritic arbour development. However, the role of PlexinA3 in the growth of dendrites of cultured cerebellar granule neurons (CGNs) is not known. We found that PlexinA3 colocalizes with CRMP2 (collapsin response mediator protein 2) in dendritic shafts. Immunoprecipitation and glutathione transferase pulldown assays showed that the intracellular Ras-binding domain of PlexinA3 directly interacts with CRMP2. PlexinA3 was necessary and sufficient for the growth of CGN dendrites, as genetic knockdown of PlexinA3 reduced but its overexpression increased dendritic lengths and dendritic tip numbers. These increases were enhanced with CRMP2 overexpression and abolished with CRMP2 knockdown, indicating that CRMP2 is the downstream effector. Furthermore, PlexinA3/CRMP2 signalling contributed to Sema3A-controlled dendritic growth. Together, these data identify a novel PlexinA3/CRMP2 pathway in semaphorin-regulated growth of cultured CGN dendrites.
    MeSH term(s) Cells, Cultured ; Interneurons ; Semaphorin-3A ; Semaphorins ; Signal Transduction
    Chemical Substances Semaphorin-3A ; Semaphorins
    Language English
    Publishing date 2020-02-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 196739-3
    ISSN 1873-7544 ; 0306-4522
    ISSN (online) 1873-7544
    ISSN 0306-4522
    DOI 10.1016/j.neuroscience.2020.02.008
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  9. Article: Surface oxygen vacancies promoted Pt redispersion to single-atoms for enhanced photocatalytic hydrogen evolution

    Cai, Jinmeng / Cao, Ang / Wang, Zhenbin / Lu, Siyu / Jiang, Zheng / Dong, Xi-Yan / Li, Xingang / Zang, Shuang-Quan

    Journal of materials chemistry A. 2021 June 22, v. 9, no. 24

    2021  

    Abstract: Isolating metal atoms on supports for catalysis has attracted great attention of researchers due to the unique catalytic properties. Here we show by utilizing the hydrogen spillover effect at high temperature (700 °C) that the in situ formed surface ... ...

    Abstract Isolating metal atoms on supports for catalysis has attracted great attention of researchers due to the unique catalytic properties. Here we show by utilizing the hydrogen spillover effect at high temperature (700 °C) that the in situ formed surface oxygen vacancies on TiO₂ nanobelts can facilitate the redispersion of Pt nanoparticles to stable single-atoms. The isolated Pt atoms are firmly confined by the surface oxygen vacancy sites in the internal surface of TiO₂. Density functional theory (DFT) calculations have further proved that Pt atom is likely to be confined to oxygen vacancies to form single-atom sites. The as-obtained catalyst exhibits excellent photocatalytic water splitting performance with a hydrogen evolution rate of 38.33 mmol mgPₜ⁻¹ h⁻¹ under simulated solar light irradiation, which is about 59.9 times higher than that of TiO₂ nanobelts with Pt nanoparticles. This approach provides a facile method to prepare noble metal catalysts with both high atom economy and reaction activity.
    Keywords catalysts ; density functional theory ; hydrogen ; hydrogen production ; irradiation ; lighting ; oxygen ; photocatalysis ; temperature
    Language English
    Dates of publication 2021-0622
    Size p. 13890-13897.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ZDB-ID 2702232-8
    ISSN 2050-7496 ; 2050-7488
    ISSN (online) 2050-7496
    ISSN 2050-7488
    DOI 10.1039/d1ta01400e
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Different fusion tags affect the activity of ubiquitin overexpression on spastin protein stability.

    Zou, Jianyu / Cai, Zhenbin / Liang, Zhi / Liang, Yaozhong / Zhang, Guowei / Yang, Jie / Zhang, Yunlong / Lin, Hongsheng / Tan, Minghui

    European journal of histochemistry : EJH

    2021  Volume 65, Issue 4

    Abstract: Spastin is one of the proteins which lead to hereditary spastic paraplegia (HSP), whose dysfunction towards microtubule severing and membrane transporting is critically important. The present study is to elucidate the mechanisms of the protein stability ... ...

    Abstract Spastin is one of the proteins which lead to hereditary spastic paraplegia (HSP), whose dysfunction towards microtubule severing and membrane transporting is critically important. The present study is to elucidate the mechanisms of the protein stability regulation of spastin. The ubiquitin encoding plasmids are transfected into COS-7 cells with different fusion tags including Green Fluorescent Protein (GFP), mCherry and Flag. The expression level of spastin was detected, microtubule severing activity and neurite outgrowth were quantified. The data showed that ubiquitin overexpression significantly induced the decreased expression of spastin, suppressed the activity of microtubule severing in COS-7 cells and inhibited the promoting effect on neurite outgrowth in cultured hippocampal neurons. Furthermore, when modulating the overexpression experiments of ubiquitin, it was found that relatively small tag like Flag, but not large tags such as GFP or mCherry fused with ubiquitin, retained the activity on spastin stability. The present study investigated the effects of small/large tags addition to ubiquitin and the novel mechanisms of post-transcriptional modifications of spastin on regulating neurite outgrowth, in the attempt to experimentally elucidate the mechanisms that control the level or stability of spastin in hereditary spastic paraplegia.
    MeSH term(s) Animals ; COS Cells ; Chlorocebus aethiops ; Protein Stability ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/genetics ; Spastin/biosynthesis ; Spastin/genetics ; Ubiquitin/biosynthesis ; Ubiquitin/genetics
    Chemical Substances Recombinant Fusion Proteins ; Ubiquitin ; Spastin (EC 3.6.4.3) ; SPAST protein, human (EC 5.6.1.1)
    Language English
    Publishing date 2021-12-07
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1109511-8
    ISSN 2038-8306 ; 0391-7258 ; 1121-4201 ; 1121-760X
    ISSN (online) 2038-8306
    ISSN 0391-7258 ; 1121-4201 ; 1121-760X
    DOI 10.4081/ejh.2021.3352
    Database MEDical Literature Analysis and Retrieval System OnLINE

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