RESUMO
The present study aimed to investigate the changes of Rho-associated kinase (Rho-kinase) and neuronal nitric oxide synthase (nNOS) expression in age-associated erectile dysfunction (ED) in Sprague-Dawley (SD) rats. A total of 100 intact male SD rats were divided into 20 groups according to their age (5-24 months; rats that were the same age in months were in the same group). Erectile response measurements were performed and the functional index intracavernosal pressure/mean arterial pressure (ICP/MAP) was tested, followed by detection of Rho-kinase and nNOS protein by western blot analysis. Finally, correlation analyses of the association between ICP/MAP and Rho-kinase, nNOS, or nNOS/Rho-kinase, as well as between age and nNOS or Rho-kinase, were performed. The functional index ICP/MAP decreased with age in SD rats. Moreover, the expression of nNOS protein decreased, while Rho-kinase expression increased, indicating that the nNOS/Rho-kinase ratio decreased with age. The Pearson's correlation coefficients for the association between ICP/MAP and Rho-kinase, nNOS and nNOS/Rho-kinase ratio were -0.917, 0.853 and 0.937, respectively (P<0.01). Furthermore, nNOS was found to be significantly negatively correlated with age (r=-0.855; P<0.01), whereas Rho-kinase was positively correlated with age (r=0.943; P<0.01). Age-associated ED was therefore correlated with decreased nNOS and increased Rho-kinase, indicating that the nNOS/Rho-kinase ratio may be used as a candidate indicator of age-associated ED.
RESUMO
The present study aimed to investigate the potential mechanisms used during signal transduction by M3 muscarinic acetylcholine receptor (CHRM3) in prostate cancer. The microarray datasets of GSE3325, including 5 clinically localized primary prostate cancers and 4 benign prostate tissues, were downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in primary prostate cancer tissues compared with benign controls were screened using the Limma package. Gene Ontology and pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. Next, a protein-protein interaction (PPI) network was constructed. Additionally, microRNAs (miRNAs) associated with DEGs were predicted and miRNA-target DEG analysis was performed using a Web-based Gene Set Analysis Toolkit. Finally, the PPI network and the miRNA-target DEG network were integrated using Cytoscape. In total, 224 DEGs were screened in the prostate cancer tissues, including 113 upregulated and 111 downregulated genes. CHRM3 and epidermal growth factor (EGF) were enriched in the regulation of the actin cytoskeleton. EGF and v-myc avian myelocytomatosis viral oncogene homolog (Myc) were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway. EGF with the highest degree of connectivity was the hub node in the PPI network, and miR-34b could interact with Myc directly in the miRNA-target DEG network. EGF and Myc may exhibit significant roles in the progression of prostate cancer via regulation of the actin cytoskeleton and the MAPK signaling pathway. CHRM3 may activate these two pathways in prostate cancer progression. Thus, these two key factors and pathways may be crucial mechanisms during signal transduction by CHRM3 in prostate cancer.