The role of Vav3 expression for inflammation and cell death during experimental myocardial infarction

Abstract Objectives Myocardial Infarction (MI) is the leading cause of chronic heart failure. Previous studies have suggested that Vav3, a receptor protein tyrosine kinase signal transducer, is associated with a variety of cellular signaling processes such as cell morphology regulation and cell transformation with oncogenic activity. However, the mechanism of Vav3-mediated MI development requires further investigation. Method Here, The authors established an MI rat model by ligating the anterior descending branch of the left coronary artery, and an MI cell model by treating cardiomyocytes with H2O2. Microarray analysis was conducted to identify genes with differential expression in heart tissues relevant to MI occurrence and development. Vav3 was thus selected for further investigation. Results Vav3 downregulation was observed in MI heart tissue and H2O2-treated cardiomyocytes. Administration of Lentiviral Vav3 (LV-VAV3) in MI rats upregulated Vav3 expression in MI heart tissue. Restoration of Vav3 expression reduced infarct area and ameliorated cardiac function in MI rats. Cardiac inflammation, apoptosis, and upregulation of NFκB signal in heart tissue of MI animals were assessed using ELISA, TUNEL staining, real-time PCR, and WB. Vav3 overexpression reduced cardiac inflammation and apoptosis and inhibited NFκB expression and activation. Betulinic Acid (BA) was then used to re-activate NFκB in Vav3-overexpressed and H2O2-induced cardiomyocytes. The expression of P50 and P65, as well as nuclear P65, was significantly increased by BA exposure. Conclusions Vav3 might serve as a target to reduce ischemia damage by suppressing the inflammation and apoptosis of cardiomyocytes.

Effect of Rheb1 in the Development of Mouse Megakaryocyte-Erythroid Progenitor Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Rheb1 in the development of mouse megakaryocyte-erythroid progenitor cells and its related mechanism.@*METHODS@#Rheb1 was specifically knocked-out in the hematopoietic system of Vav1-Cre;Rheb1fl/fl mice(Rheb1Δ/Δ mice). Flow cytometry was used to detect the percentage of red blood cells in peripheral blood and erythroid cells in bone marrow in Vav1-Cre;Rheb1fl/fl mice and control mice. The CFC assay was used to detect the differentiation ability of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Real-time fluorescence quantification PCR was used to detect the relative expression of PU.1,GATA-1,GATA-2,CEBPα and CEBPβ of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Rapamycin was added to the culture medium, and it was used to detect the changes in cloning ability of megakaryocyte-erythroid progenitor cells from wild-type mice in vitro.@*RESULTS@#After Rheb1 was knocked out, the development and stress response ability of megakaryocyte-erythroid progenitor cells in mice were weaken and the differentiation ability of megakaryocyte-erythroid progenitor cells in vitro was weaken. Moreover, the expression of GATA-1 of megakaryocyte-erythroid progenitor cells was decreased. Further, rapamycin could inhibit the differentiative capacity of megakaryocyte-erythroid progenitor cells in vitro.@*CONCLUSION@#Rheb1 can regulate the development of megakaryocyte-erythroid progenitor cells probably through the mTOR signaling pathway in mice.

The function of Vav protein in immune system / 国际儿科学杂志

Vav-family proteins are guanosine nucleotide exchange factors(GEFs)and one of RhoGEFs family numbers.Vav proteins can influence cell signaling transduction, cytoskeleton recombination and adherence migration in special cells by RhoA, RhoG and Rac-1 pathway.There are 80 kinds of RhoGEFs in mammalian cell.Vav proteins play an important role in hematological system, nervous system, cardiovascular system and immune system.So the function of vav protein in immune system was reviewed in this paper.

The function of Vav protein in immune system / 国际儿科学杂志

Vav-family proteins are guanosine nucleotide exchange factors (GEFs) and one of RhoGEFs family numbers.Vav proteins can influence cell signaling transduction,cytoskeleton recombination and adherence migration in special cells by RhoA,RhoG and Rac-1 pathway.There are 80 kinds of RhoGEFs in mammalian cell.Vav proteins play an important role in hematological system,nervous system,cardiovascular system and immune system.So the function of vav protein in immune system was reviewed in this paper.

The expression of Vav1 and its correlation with prognosis in patients with gastric cancer / 天津医药

Objective To investigate the expression of Vav1 in gastric cancer(GC), and analyze its potential relevance to clinicopathological characteristics and prognostic significance in GC patients. Methods The mRNA expression level of Vav1 was detected by real-time quantitative PCR in GC cell lines (HGC-27,SGC7901 and MGC803) and normal gastric mucosa cell line (GES-1). In addition, the protein expression of Vav1 was analyzed by immunohistochemistry in formalin-fixed samples from 105 GC patients. The associations between clinical pathological features and Vav1 protein expression were evaluated in GC patients. Kaplan-Meier method and Cox regression analysis were used to analyze the related factors influencing the prognosis of GC. Results The mRNA expression levels of Vav1 were significantly higher in GC cell lines (HGC-27, SGC7901, MGC803) than those in normal gastric mucosa cell line (GES-1, P<0.05). The positive expression of Vav1 in GC tissues was correlated with diameter of tumor and lymph node metastasis (P<0.05). The univariate analysis showed that size of tumor, degree of differentiation, serosal invasion, lymph node metastasis and Vav1 expression were significantly related with prognosis of GC (P<0.05). Results of Cox regression showed that tumor invasion depth (HR=2.764, 95%CI 1.316-5.817, P=0.007), lymph node metastasis (HR=1.298, 95%CI 1.098-1.534, P=0.002) and Vav1 expression (HR=2.577, 95%CI 1.066-3.946, P=0.006) were the risk factors affecting prognosis of patients with gastric cancer. Conclusion Vav1 performs important role in the aggressiveness of GC, and Vav1 may serve as a novel prognostic factor in GC.

Effect of Vav3 gene inhibition on inhibitor of apoptosis proteins and multidrug resistance in gastric cancer cells / 第二军医大学学报

Objective To explore the role of Vav3 gene in multidrug resistance (MDR) of gastric cancer and the related mechanism. Methods QRT-PCR was used to examine the expressions of Vav3 gene in gastric cancer tissues, tumor-adjacent tissues, human gastric cancer cell line SGC7901, and gastric epithelial cell line GES-1. Then Vav3-siRNA was synthesized and tansfected into SGC7901 cells. MTT assay was then used to determine the inhibition rates of tumor cells exposed to chemotherapeutic agents (5-FU, L-OHP) before and after Vav 3-siRNA transfection. Realtime RT-PCR and Western blotting analysis were used to observe the expressions of inhibitor of apoptosis proteins (IAPs) : xIAP, Survivin, and Livin; meanwhile, the expression and activity of Caspase-3 and Caspase-8 were also determined. Results Vav3 was over-expressed in gastric cancer tissues and gastric cell line compared with those in tumo-adjacent tissues and gastric epithelial cell line GES-1 (P<0.05). Expression of Vav3 was significantly inhibited by Vav3-siRNA (P<0.01). Inhibition rates of tumor cells exposed to 5-FU and L-OHP were significantly increased 48 h after Vav3-siRNA tansfection (P<0.05). The expressions of xIAP and Survivin were significantly decreased in cancer cells after Vav3-siRNA tansfection (both P<0.05), and no notable change was found for Livin expression; also the expression and activity of Caspase-3 and Caspase-8 protein were significantly increased after Vav3-siRNA tansfection in SGC7901 cells (all P<0.05). Conclusion Vav3 can participate in MDR of gastric cancer by regulating apoptotic pathways, and inhibition of Vav3 can help reverse MDR of gastric cancer cells by regulating some IAPs.

Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions

BACKGROUND: The role of small GTPase molecules is poorly understood under high glucose conditions. METHODS: We analyzed the expression pattern of Vav3 in skeletal muscle C2C12 cells under high glucose culture condition with reverse transcription-polymerase chain reaction and Western blot analysis. We also measured glucose uptake using isotope-labelled glucose. RESULTS: We showed that expression of Vav3 (a guanine nucleotide exchange factor for RhoA) increased. mRNA and protein levels in skeletal muscle C2C12 cells under high glucose conditions. The AMP-activated protein kinase (AMPK) activator AMPK agonist 5-aminoimidazole-4-carboxy-amide-1-d-ribofuranoside (AICAR) suppressed high glucose-induced Vav3 induction. In addition, exposure of cells to high glucose concentration increased the phosphorylation of PAK-1, a molecule downstream of RhoA. The phosphorylation of paxillin, a downstream molecule of PAK-1, was also increased by exposure to high glucose. Phosphorylation of these molecules was not observed in the presence of AICAR, indicating that AMPK is involved in the RhoA signal pathway under high glucose conditions. Knock down of Vav3 enhances metformin-mediated glucose uptake. Inhibition of AMPK blocked the increases of Vav3 knock down-induced glucose uptake. Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake. CONCLUSION: These results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation.

Efecto de la proteína E2 del virus de hepatitis C sobre la activación de células NK / Effect of E2 protein of hepatitis C virus on the activation of NK cells

En estudios previos, se ha descrito un disminución de la activación y actividad citotóxica de las células NK en los pacientes infectados con hepatitis C; sin embargo, se desconoce el mecanismo por el cual éste fenómeno ocurre. En el presente reporte se estudió el efecto de la proteína E2 de la envoltura del virus o de la estimulación de su receptor con el anticuerpo anti-CD81 sobre la fosforilación de tirosinas, serinas, las enzimas: proteína quinasa C y fosfoinositol 3 quinasa, el factor de transcrición Nfkb y el intercambiador de nueclotidos VAV de células NK de controles normales estimulados con anti-CD16. Ambos, la proteína E2 y anti-CD81, combinado o por separado inducen una disminución de la fosforilación de tirosinas y serinas, así como una marcada disminución de la fosforilación de PKC, NFkB, PI3K y en menor grado VAV. Se concluye que la proteína E2 sola y en conjunto con anti-CD81 inducen señales inhibitorias responsables de la disminución en la activación de las células NK de pacientes infectados por el VHC y que éste fenómeno puede ser responsable de la cronicidad que se reporta en dicha enfermedad

The decrease in NK cell activation and cytotoxic activity in patients infected with hepatitis C virus has been described; however, the mechanism by whcih this phenomenon occurs is not known. In the present report, the effect of the E2 protein of the virus envelope or the stimulation of its receptor CD81 with the antibody anti-CD81 on the phosphorylation of tyrosines, serine, the enzymes protein kinase C, phosphoinositol kinase 3 (PI3K), the transcription factor NfkB and the nucleotide exchange protein VAV was assessed in NK cells from normal controls stimulated with anti-CD16. Both the protein E2 and anti-CD81 by themselves or combined, generated a decrease in tyrosine, serine, and a marked decrease in the phosphorylation of PKC, NfkB, PI3k and in less extent in VAV. It is concluded that the E2 protein alone and combined with anti-CD81 induce inhibitory signals responseible for the decrease in the activation of NK cells of infected HCV patients and it could be responsible for the chronicity observed in this disease

Progress in Vav3 and breast cancer research / 国际肿瘤学杂志

Vav3 oncogene is a member of the Vav family. Vav3 protein contains multiple functional motifs and is involved in cancer development and progression through its role in various cellular signaling processes, including cytoskeleton organization, calcium influx, genetic transcription, cell transformation, proliferation and apoptosis. In addition, Vav3 interacts with estrogen receptor and enhances ERα-mediated signaling axis, therefore plays an important role in breast cancer.

Effect of RetroNectin on the Proliferation of CIK Cells and the Possible Mechanisms / 中国肿瘤临床

Objective: To investigate the effect of RetroNectin on CIKs cells and the related mechanisms. Methods: Peripheral blood mononuclear cells (PBMC) were collected from patients and divided into two groups: group Ⅰ and group Ⅱ. Samples in group Ⅰ were seeded into culture flask precoated with RetreNec-tin and CD3mAb to induce CIKs. While samples in group Ⅱ were seeded into common culture flask. The pro-liferation of CIKs was detected by cytometric analysis. The cytotoxic activity of CIKs was determined by LDH assays. The phenotype changes and cell cycle of CIKs were identified by flow cytometry. The apoptosis of cells was detected by Annexin V/PI. Western blot was employed to detect the level of protein Vav1. The CD49d and CD49e were blocked by anti-CD49d and anti-CD49e and the proliferation of cells was tested by cytometric analysis after the blockage. The phenotype changes of cells were identified by flow cytometry after the blockage. Results: RetroNectin enhanced the proliferation of CIKs (P<0.05). Flow cytometric analysis showed that RetroNectin significantly increased the number of CD25+ T cells (P<0.05). RN-CIK was more ac-tive than CIK in killing HCT-8 cell lines in vitro (P<0.05). RetroNectin could block the CIKs at G_1 phase (P<0.05) and resist apoptosis. There was no significant difference in the proliferation between the two groups af-ter the blockage with CD49d and CD49e (P>0.05). The expression of protein Vavl was associated with CD25+T cells. Conclusion: RetroNectin enhances the proliferation of CIKs by influencing the cell cycle, resist-ing apoptosis possibly through the site of CD49d and CD49e, and inducing T cell activation as the second sig-naling through Vav1.

Laboratory ventilation technique and its control system / 医疗卫生装备

Based on the description of styles and characteristics of fume hoods in modern laboratories, this paper analyzes the control strategies in fume hoods and ventilation systems and discusses the control and application of VAV as well as its advantages on safety, energy conservation and comfort.