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2.
Sci Rep ; 8(1): 2760, 2018 02 09.
Article in English | MEDLINE | ID: mdl-29426889

ABSTRACT

Engineered silica nanoparticles (NPs) have attracted increasing interest in several applications, and particularly in the field of nanomedicine, thanks to the high biocompatibility of this material. For their optimal and controlled use, the understanding of the mechanisms elicited by their interaction with the biological target is a prerequisite, especially when dealing with cells particularly vulnerable to environmental stimuli like neurons. Here we have combined different electrophysiological approaches (both at the single cell and at the population level) with a genomic screening in order to analyze, in GT1-7 neuroendocrine cells, the impact of SiO2 NPs (50 ± 3 nm in diameter) on electrical activity and gene expression, providing a detailed analysis of the impact of a nanoparticle on neuronal excitability. We find that 20 µg mL-1 NPs induce depolarization of the membrane potential, with a modulation of the firing of action potentials. Recordings of electrical activity with multielectrode arrays provide further evidence that the NPs evoke a temporary increase in firing frequency, without affecting the functional behavior on a time scale of hours. Finally, NPs incubation up to 24 hours does not induce any change in gene expression.


Subject(s)
Action Potentials/drug effects , Nanoparticles , Neuroendocrine Cells/drug effects , Neurons/metabolism , Silicon Dioxide/pharmacology , Animals , Cell Line , Gene Expression/drug effects , Hypothalamus/cytology , Mice , Neuroendocrine Cells/physiology , Neurons/drug effects
3.
Curr Med Chem ; 19(24): 4059-67, 2012.
Article in English | MEDLINE | ID: mdl-22834796

ABSTRACT

The involvement of Chromogranin A (CgA) in the cardiovascular function regulation is attributed to its function as a prohormone. Several studies indicated that CgA-derived peptides, particularly Vasostatin-1 (VS-1) and Catestatin (CST), exert signaling effects in numerous organs/systems, including the cardiovascular system. This review focuses on the recently described signaling pathways activated by VS-1 and CST, giving insights into the mechanisms at the basis of their cardiac negative inotropic action, their vasodilator effects and their cardioprotective role observed in different experimental conditions. Accumulated evidences provided convincing support for VS-1 and CST as vasoactive peptides indirectly acting on cardiomyocytes through a Ca(2+)-independent/PI3-K-dependent NO release from endothelial cells. This pathway is supposed to be triggered by the interaction of these peptides with the plasma membrane. The premise of these studies grounds on the biochemical features of VS-1 and CST, which are structurally characterized by amphipathic properties and the ability to interact with mammalian and microbial membranes. On the other hand, recent data obtained in both isolated heart and isolated cardiomyocytes suggest that the VS-1 and CST-mediated cardioprotective effects are primarily direct on the myocardium, rather than endothelium-dependent. Anyway, both direct and indirect pathways seem to be characterized by the absence of specific membrane receptors on target cells, highlighting intriguing novelties in the topic of cell signaling, in particular respect to an hypothetical receptor-independent eNOS activation.


Subject(s)
Chromogranin A/metabolism , Endothelium, Vascular/metabolism , Peptide Fragments/metabolism , Endocytosis , Humans , Myocytes, Cardiac/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Signal Transduction
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