Anti-GNAS polyclonal antibody

Essential hypertension (EH) is a major risk factor for cardiovascular disease. Despite considerable efforts to elucidate the pathogenesis of EH, there is an imperious need for novel indicators of EH. This study aimed to develop a method to predict potential biomarkers of EH from the point of view of network. A pathway-based gene-gene interaction (GGI) network model was constructed and analyzed, containing 116 nodes and 1272 connections. The nodes represented EH-related genes, and that connections represented their interactions. The network showed a small-world property and uneven degree distribution, suggesting that a few highly interconnected hubs played a vital role in EH. An inherent hierarchy and assortative mixing pattern were also observed in the network. GNAS, GNB3, PF4 and PPBP showed the highest values of degrees and centrality indices, and were chosen as potential biomarkers of EH. A two-mode network model based on the potential biomarkers demonstrated that hemostasis and GPCR ligand binding pathway were key pathways contributing to EH. Results of this study improve our current understanding of the molecular mechanisms driving EH. The selected genes and pathways have the potential to be used in the diagnosis and treatment of EH. Moreover, the combination of pathway analysis and complex network methodology provides a novel strategy for searching new genetic indicators of complex diseases.

Testosterone is an anabolic androgenic steroid hormone involved in brain development, reproduction, and social behavior. Several studies have shown that testosterone can cause impulsivity in humans, which in turn, is linked with mood-related psychiatric disorders and higher risk of death by suicide. The mechanisms by which testosterone abuse influences impulsivity are unclear. The present study aims to understand how testosterone influences impulsivity in a rodent model both at behavioral and molecular levels. In this study, rats were either only gonadectomized or gonadectomized and injected with supraphysiological doses of testosterone. Their relative impulsivity levels were assessed using the go/no-go task. Serum level of testosterone was measured using ELISA. Transcript levels of alpha-2A adrenergic receptor (Adra2a), G proteins (stimulatory subunit-G(s) [Gnas], inhibitory subunit-G(i) [Gnai1 and Gnai2]), and catalytic and regulatory subunits of protein kinase A (PKA) were examined using quantitative PCR (qPCR) in brain areas associated with limbic system (prefrontal cortex (PFC), hippocampus, and amygdala). The testosterone-treated (T) group showed significantly higher level of serum testosterone and displayed a lower go/no-go ratio, indicating greater impulsivity compared to the gonadectomized (GDX) group. The transcript levels Adra2a and G(s) genes and PKA subunits encoded by Prkar1a, Prkar1b, Prkar2a, and Prkaca genes were significantly upregulated in PFC of testosterone treated rats. The expression levels of these genes were not significantly altered in hippocampus. On the other hand, amygdala showed changes only in Gnas and Prkar2a. These results suggest that chronic testosterone influences impulsivity possibly via hyperactive alpha-2A adrenergic receptor-PKA signaling axis, specifically in the PFC.