Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) 3ε, CD3γ, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.
Animals ; Cannabinoids ; Cerebellar Diseases* ; Cerebellum ; Glutamic Acid ; Homeostasis ; Immunosuppression* ; Mice* ; Neurons ; R-SNARE Proteins ; T-Lymphocytes ; Tetanus ; Tetanus Toxin

Membrane microparticles are shed from the plasma membrane of most eukaryotic cells when these cells were undergone activation or apoptosis, and released into the extracellular environment. Their composition depends on the cellular origin and processes triggering their formation. Several lines of evidence suggest that membrane microparticles might be able to facilitate cell-cell cross-talk and play an important roles in the regulation of survival, proliferation, differentiation, adhesion and chemotaxis of hematopoietic cells. Here, the components, mechanism of formation and the regulatory roles of membrane microparticles in hematopoiesis were reviewed.
Caveolae ; metabolism ; physiology ; Cell Membrane ; metabolism ; physiology ; Hematopoiesis ; physiology ; Humans ; Models, Biological ; R-SNARE Proteins ; metabolism ; physiology

PURPOSE: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. METHODS: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. RESULTS: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p=0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p < 0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. CONCLUSION: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.
Autophagy ; Biomarkers ; Breast Neoplasms* ; Breast* ; Humans ; Logistic Models ; Lymph Nodes ; Mammary Glands, Human ; Membrane Fusion ; Methods ; N-Ethylmaleimide-Sensitive Proteins ; Neoplasm Metastasis ; Prognosis ; R-SNARE Proteins* ; Recurrence

OBJECTIVETo investigate the association of synaptobrevins/vesicle-associated membrane proteins 8 (VAMP8) gene rs1010 polymorphism with coronary heart disease (CHD) in Chinese Han population.

METHODSThe allele and genotype frequencies of the VAMP8 gene rs1010 locus in 185 CHD patients and 149 controls were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing.

RESULTSThere was polymorphism of the VAMP8 gene rs1010 locus in the studied population. The distribution of VAMP8 genotypes was in Hardy-Weinberg equilibrium. The frequency of the A allele in the CHD group was significantly higher than that in control (67.3% vs 53.0%, P< 0.05). Multiple logistic regression analysis showed that genotypes AA and AG were independent risk factors of coronary heart disease. The odds ratio (OR) of (AA+AG) genotype versus GG genotype was 1.969,95% CI: 1.032-3.755.

CONCLUSIONThe VAMP8 rs1010 polymorphism was associated with CHD risk in Chinese Han population, the A allele might serve as a genetic risk factor of coronary heart disease.

Aged ; Asian Continental Ancestry Group ; genetics ; Coronary Disease ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; genetics ; R-SNARE Proteins ; genetics

Autophagy is an evolutionarily-conserved self-degradative process that maintains cellular homeostasis by eliminating protein aggregates and damaged organelles. Recently, vesicle-associated membrane protein-associated protein B (VAPB), which is associated with the familial form of amyotrophic lateral sclerosis, has been shown to regulate autophagy. In the present study, we demonstrated that knockdown of VAPB induced the up-regulation of beclin 1 expression, which promoted LC3 (microtubule-associated protein light chain 3) conversion and the formation of LC3 puncta, whereas overexpression of VAPB inhibited these processes. The regulation of beclin 1 by VAPB was at the transcriptional level. Moreover, knockdown of VAPB increased autophagic flux, which promoted the degradation of the autophagy substrate p62 and neurodegenerative disease proteins. Our study provides evidence that the regulation of autophagy by VAPB is associated with the autophagy-initiating factor beclin 1.
Autophagy ; drug effects ; physiology ; Beclin-1 ; genetics ; metabolism ; Cell Line, Transformed ; Gene Expression Regulation ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Microtubule-Associated Proteins ; genetics ; metabolism ; R-SNARE Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; RNA-Binding Proteins ; genetics ; metabolism ; Transfection

Amyotrophic Lateral Sclerosis ; genetics ; Animals ; Biological Transport, Active ; Bipolar Disorder ; genetics ; Glucose Transporter Type 4 ; metabolism ; Hepacivirus ; physiology ; Humans ; Neoplasm Metastasis ; Neoplasms ; metabolism ; Point Mutation ; Polymorphism, Single Nucleotide ; R-SNARE Proteins ; metabolism ; Tissue Distribution ; Transport Vesicles ; physiology ; Vesicular Transport Proteins ; chemistry ; genetics ; metabolism ; physiology ; Virus Replication