Showing papers by "Alessandra Stacchiotti published in 2012"
TL;DR: This is the first demonstration that taurine enhances autophagic protection against apoptosis by reducing ER stress, thus making it possible to develop new strategies to reduce severe cisPt-induced side-effects such as nephrotoxicity.
50 citations
TL;DR: The present review is focused on the close relationship between autophagy and age- related disorders in different tissues/organs and in transgenic animal models and comments on the up to date literature on mechanisms responsible for age-related impairment of autophagic regulation.
32 citations
TL;DR: Melatonin use could be a safe strategy of improving the development and progression of atherosclerosis and the antioxidant effects of melatonin are both on antioxidant enzymes and other proteins, such as CyPA, which will be considered the bridge between inflammation and Atherosclerosis.
Abstract: Atherosclerosis is a chronic disease of the arterial wall and a leading cause of death and loss of productive life years worldwide. It is considered a chronic inflammatory vascular disease characterized of monocyte extravasation into the arterial wall (Libby et al., 2011). Researches into the disease have led to many compelling hypotheses about the pathophysiology of atherosclerotic lesion formation and of complications such as myocardial infarction and stroke (Ross, 1999). The last several decades have witnessed aburgeoning growth of understanding of the molecular pathways involved in atherogenesis, atherosclerotic lesion progression and the pathogenetic mechanisms involved. In this study was evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis, the beneficial effects of melatonin in vascular remodelling due to its ability to modulate rolling of mononuclear cells and its acting on vascular smooth muscle cell proliferation and neointima formation. In particular, in this study APOE null mice at 6 and 15 weeks of age were used; they were treated with melatonin at dose of 0.1mg/kg/day and 10mg/kg/day. We evaluated both CyPA expression and its signaling pathways in atherosclerosis development. CyPA expression increased in mononuclear cells and, in turn, stimulated vascular cell adhesion and interleukin-6 increase in the endothelial cells and vascular smooth muscle cells in a time-dependent manner. Melatonin treatment at the dose of 10mg/ kg/day completely improved vascular injury inhibiting the increase of CyPA. In summary, these findings suggest that CyPA induces the early step of atherosclerosis and indicate that the antioxidant effects of melatonin are both on antioxidant enzymes and other proteins, such as CyPA. Moreover, CyPA will be considered the bridge between inflammation and atherosclerosis. Thus, melatonin use could be a safe strategy of improving the development and progression of atherosclerosis.
TL;DR: Novel data suggest that, under basal conditions, Rvs may regulate proximal tubular polarity, lysosomes and mitochondria distribution and that to validate the efficacy of dietary of EAAm combined with Rvs therapy further studies on the renal function are mandatory.
Abstract: Rosuvastatin (Rvs) represents one of the most used cholesterol-lowering statins even if its effects may be wider than simply regulation of lipids metabolism [1]. Despite the efficacy in preventing cardiovascular diseases, long-term delivery of statins is associated to adverse effects [2]. So here we studied healthy normotensive mice fed with Rvs at a therapeutic dose (20 mg/kg/day) for one month. To evaluate the influence of dietary essential amino acids mixture (EAAm) in this model, other mice were fed with Rvs and EAAm daily for one month. A normal rodent chow or EAAm supplementation for the same period were further administered in control groups. Ultrastructural analysis of the glomerular filtration barrier did not show any difference between groups. Glomerular area together with mitochondria and lysosomal parameters in renal tubules were evaluated. Moreover we focused on the distribution of chaperones and mitochondria markers (Grp75, Grp78, Bcl2), nitric oxide isoforms (iNOS and eNOS), and cell adhesion molecules (E-cadherin and β-catenin). Control groups were similar except for increased mitochondria density and Grp75 staining after EAAm diet. In contrast, Rvs attenuated Grp75/Bcl2 patterns, but enhanced Grp78 expression. Remarkably E-cadherin shifted from the basolateral to the apical side in proximal tubules while evident β-catenin signal was maintained mainly in the distal tubules and in the macula densa. However, after one month of EAAm supplementation, all parameters become almost similar to controls, except for Bcl2 that persisted at higher level. These novel data suggest that, under basal conditions, Rvs may regulate proximal tubular polarity, lysosomes and mitochondria distribution. EAAm supplementation further reinforces the tubular structure in the kidney, stimulating mitochondriogenesis, as corroborated by morphometry, intense Bcl2 and vascular eNOS expressions. However to validate the efficacy of dietary of EAAm combined with Rvs therapy further studies on the renal function are mandatory.