Search

Rosmarinus officinalis L. (RO), an aromatic plant used as food condiment and in traditional medicine, exerts numerous beneficial properties including antioxidant, analgesic and neuroprotective effects. Onset and progression of homeostatic imbalances observed in the early phases of a number of neurodegenerative diseases, have been associated with a gap junction (GJ)-dependent increased membrane permeability and alterations of connexins (Cxs), including Cx43. Here, we evaluate spray-dried RO extract (SDROE)-mediated effects on cell viability, apoptosis and Cx43-based intercellular communication using human SH-SY5Y neuron-like and human A-172 glial-like cells in an in vitro model of oxygen glucose deprivation (OGD) injury. We found that SDROE exerts a protective action in OGD-injured cells, increasing cell viability and metabolic turnover and decreasing Cx43-based cell coupling. These data suggest that SDROE-mediated Cx43 reduction may be the molecular basis for its beneficial effects to be exploited for preventive treatment against the risk of some neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Cell-to-cell interaction and cell-to-extracellular environment communication are emerging as new therapeutic targets in neurodegenerative disorders. Dynamic expression of connexins leads to distinctive hemichannels and gap junctions, characterized by cell-specific conduction, exchange of stimuli or metabolites, and particular channel functions. Herein, we briefly reviewed classical physiological traits and functions of connexins, hemichannels, and gap junctions, in order to discuss the controversial role of these proteins and their mediated interactions during neuroprotection, with a particular focus on Cx43-based channels. We pointed out the contribution of connexins in neural cells populations during neurodegenerative processes to explore potential neuroprotective therapeutic applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the product of accumulated genetic and epigenetic alteration where tumor cells support each other through cellular communication mechanisms and deregulated signalling processes. The autocrine and paracrine pathways between the intracellular and extracellular milieu is mediated by connexin 43, the main gap junction-forming protein driving glioblastoma progression. In this scenario, sonic hedgehog pathway, a key deregulated pathway involved in cell network signalling may affect connexin 43 expression, promoting glioblastoma pathobiology. In this study, we sought to explore how the modulation of the sonic hedgehog affects connexin 43 inducing glioblastoma hallmarks. To do this we evaluated biological effects of sonic hedgehog pathway modulation by purmorphamine and cyclopamine, a smoothened agonist and antagonist, respectively. We revealed that cell migration and proliferation are associated with connexin 43 expression upon sonic hedgehog modulation. Our study suggests that sonic hedgehog and connexin 43 axis may represent a potential therapeutic strategy for glioblastoma. Glioblastoma (GBM) represents the most common primary brain tumor within the adult population. Current therapeutic options are still limited by high rate of recurrences and signalling axes that promote GBM aggressiveness. The contribution of gap junctions (GJs) to tumor growth and progression has been proven by experimental evidence. Concomitantly, tumor microenvironment has received increasing interest as a critical process in dysregulation and homeostatic escape, finding a close link between molecular mechanisms involved in connexin 43 (CX43)-based intercellular communication and tumorigenesis. Moreover, evidence has come to suggest a crucial role of sonic hedgehog (SHH) signalling pathway in GBM proliferation, cell fate and differentiation. Herein, we used two human GBM cell lines, modulating SHH signalling and CX43-based intercellular communication in in vitro models using proliferation and migration assays. Our evidence suggests that modulation of the SHH effector smoothened (SMO), by using a known agonist (i.e., purmorphamine) and a known antagonist (i.e., cyclopamine), affects the CX43 expression levels and therefore the related functions. Moreover, SMO activation also increased cell proliferation and migration. Importantly, inhibition of CX43 channels was able to prevent SMO-induced effects. SHH pathway and CX43 interplay acts inducing tumorigenic program and supporting cell migration, likely representing druggable targets to develop new therapeutic strategies for GBM. [ABSTRACT FROM AUTHOR]

In this study, a new gap junction (GJ) connexin (Cx) gene was isolated from the neural tube of chicken (c) embryos (HH21) and cloned by degenerate reverse transcription–polymerase chain reaction (RT-PCR). The open reading frame of the gene encodes for a protein of 343 amino acid residues with strong similarity to highly conserved connexin sequences. On the basis of the predicted molecular mass of 39,144 kDa, we denominated it as cCx39. Sequence analysis allocated the cCx39 to the α-group of connexin gene family. The mRNA expression of cCx39 was detected by RT-PCR and Northern blot in several tissues of chicken, including different parts of central nervous system, heart, liver, kidney, aorta and ovary. In situ hybridisation analysis of chicken brain showed strong expression in neurons of granular layers of cerebellum, optic tectum and ectostriatum. The in situ hybridisation of extracererebral tissues revealed strong expression of cCx39 in the atrium of the heart, the external layer of the aorta and endothelium of biliary vessels; moderate expression was found in the endothelium of the aorta. [Copyright &y& Elsevier]