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|description.abstract||Redox balance is important for platelet physiology, indeed it is crucial for blood coagulation and thrombosis. This thesis will give an update on intracellular and plasma membrane systems involved on redox homeostasis in human platelets, with particular regard to vitamin C and plasma membrane NAD(P)H oxidases.
The redox balance is linked to the presence of intracellular antioxidants; in particular, vitamin C appears to be a key modulator of platelet oxidative state, since these cells physiologically accumulate ascorbic acid. Here, we showed, for the first time, that platelets could compensate for fluctuations in ascorbate levels by modulating the expression of the Na+-dependent transporter SVCT2 at translational level. Moreover, we showed that changes in intracellular ascorbic acid content had physiological relevance, since they modulate the surface sulfhydryl content and the thrombus viscoelastic properties.
Intracellular reducing equivalents can be propagated to the plasma membrane and electrons transferred to external acceptors, thus affecting both adjacent cells and circulating blood components. In platelets, the plasma membrane redox (PMR) system has not yet been fully characterized and the molecular identities of most components are unknown. Here we described the presence of at least one member of the plasma membrane hydroquinone-(NADH) oxidase family (namely Ecto-NOX1). We found that Ecto-NOX1 is sensitive to capsaicin: indeed, it is up-modulated through a mechanism requiring binding of capsaicin to its receptor, namely the transient receptor potential vanilloid subtype 1 (TRPV1). Ligand-receptor interaction triggers a signalling cascade leading to reactive oxygen species (ROS) production, which in turn enhances the expression and activity of Ecto-NOX1. Redox regulation of Ecto-NOX1 may be important for platelet recruitment and activation during inflammatory diseases.||en|
|title||Intracellular and surface redox systems in human platelets||en|
|degree.name||Biochimica e biologia molecolare||en|
|degree.discipline||Facoltà di medicina e chirurgia||en|
|degree.grantor||Università degli studi di Roma Tor Vergata||en|
|Appears in Collections:||Tesi di dottorato in medicina|
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