Doppler pulsato delle arterie arcuate intrarenali nel cane

Nel campo della medicina interna dei piccoli animali le patologie renali costitui- scono una delle principali cause di mortalità. In medicina umana numerosi lavori hanno dimostrato che lo studio del rene attra- verso la metodica doppler ad onda pulsata delle arterie arciformi e la conseguente deter- minazione dell’indice di resistività consente di ottenere delle informazioni utili per la diagnosi precoce di alcune nefropatie. Nonostante non tutti i processi patologici renali causino un’alterazione delle resi- stenze vascolari intrarenali o comunque producano un aumento rilevabile dell’indice di resistività, tale indice può risultare utile in corso di patologie renali acute e sindromi ostruttive. L ’obiettivo di questo studio è di determinare il normale range di variabilità dell’in- dice di resistività in cani sani allo scopo di valutarne, in un secondo momento, le modi- ficazioni in presenza di diverse nefropatie. Abbiamo ottenuto un valore medio di 0,61 (deviazione standard pari a 0,049) per il rene destro e di 0,60 per il rene sinistro (devia- zione standard pari a 0,046). Non sono state riscontrate differenze significative in misu- razioni seriali effettuate nello stesso rene, né tra i due reni di uno stesso soggetto mentre in soggetti diversi, sebbene sani, i valori dell’indice di resistività possono oscillare all’in- terno di un range piuttosto ampio. Inoltre non è stata riscontrata alcuna correlazione significativa tra l’età o il sesso del soggetto in esame ed il suo indice di resistività

Garlic-derived diallyl disulfide modulates peroxisome proliferator activated receptor gamma co-activator 1 alpha in neuroblastoma cells

The peroxisome proliferator activated receptor gamma co-activator 1 alpha (PGC1α) is an inducible transcriptional co-activator with direct function in the induction of mitochondrial biogenesis. In the present report we show that, in SH-SY5Y neuroblastoma cells, garlic-derived diallyl disulfide (DADS) is able to increase PGC1α expression in a ROS-dependent manner and to induce mitochondrial biogenesis at early stage of treatment that precede cell cycle arrest and apoptosis outcome. In particular, we demonstrate that DADS elicits: i) the increase of PGC1α within nuclear compartment; ii) the decrease of PGC1α non-active acetylated form; iii) the induction of nuclear-encoded mitochondrial genes such as TFAM and TFBM1. We also show an accumulation of PGC1α within mitochondria along with an increased association with the regulatory D-Loop region of mtDNA and a concomitant augmented expression of mitochondrial RNA. Such events are related to a prompt elevation of mitochondrial mass, as assessed by evaluating the content of mtDNA. We show that the induction of mitochondrial biogenesis is directed to dampen the cytotoxic effect of DADS. Indeed, PGC1α overexpression or down-regulation prevents or exacerbates mtDNA loss and apoptosis. Overall the data highlight an anti-apoptotic role of PGC1α-mediated mitochondrial biogenesis in neuroblatoma cells and suggest PGC1α as a potential target for enhancing the effectiveness of therapy in aggressive neuroblastoma with high drug-resistance

Extranuclear localization of SIRT1 and PGC-1α: an insight into possible roles in diseases associated with mitochondrial dysfunction

SIRT1 and PGC-1α are two nutrient sensing master regulators of cellular metabolism and their upregulation is often linked to increased lifespan. SIRT1 and PGC-1α modulate the expression of a set of nuclear genes controlling many metabolic pathways. In recent years mounting evidence has indicated the implication of these proteins in several mitochondrial diseases including neurodegenerative disorders, myopathies and Type II diabetes mellitus. Recently, these proteins have been localized in cytoplasm and mitochondria wherein they target novel substrates opening new insight into their possible function in modulating extranuclear genes and proteins. This review will firstly summarize the nuclear function of SIRT1 and PGC-1α. Then, data from papers demonstrating the presence of SIRT1 and PGC-1α in the cytoplasm and in mitochondria will be outlined so that these extranuclear forms do not remain out of sight. Finally, very recent evidence of the alteration of the pathways governed by SIRT1 and PGC-1α in human mitochondrial diseases will be described and the possible role of their mitochondrial forms will be briefly discussed

p53 orchestrates the PGC-1α-mediated antioxidant response upon mild redox and metabolic imbalance

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1 α (PPARGC1A or PGC-1α) is a powerful controller of cell metabolism and assures the balance between the production and the scavenging of pro-oxidant molecules by coordinating mitochondrial biogenesis and the expression of antioxidants. However, even though a huge amount of data referring to the role of PGC-1α is available, the molecular mechanisms of its regulation at the transcriptional level are not completely understood. In the present report, we aim at characterizing whether the decrease of antioxidant glutathione (GSH) modulates PGC-1α expression and its downstream metabolic pathways

Caloric Restriction and the Nutrient-Sensing PGC-1α in Mitochondrial Homeostasis: New Perspectives in Neurodegeneration

Mitochondrial activity progressively declines during ageing and in many neurodegenerative diseases. Caloric restriction (CR) has been suggested as a dietary intervention that is able to postpone the detrimental aspects of aging as it ameliorates mitochondrial performance. This effect is partially due to increased mitochondrial biogenesis. The nutrient-sensing PGC-1α is a transcriptional coactivator that promotes the expression of mitochondrial genes and is induced by CR. It is believed that many of the mitochondrial and metabolic benefits of CR are due to increased PGC-1α activity. The increase of PGC-1α is also positively linked to neuroprotection and its decrement has been involved in the pathogenesis of many neurodegenerative diseases. This paper aims to summarize the current knowledge about the role of PGC-1α in neuronal homeostasis and the beneficial effects of CR on mitochondrial biogenesis and function. We also discuss how PGC-1α-governed pathways could be used as target for nutritional intervention to prevent neurodegeneration

Shear stress induces transforming growth factor-beta 1 release by arterial endothelial cells

Myointimal hyperplasia is a common complication after vascular reconstruction. Increasing shear stress has been shown to reduce formation of myointimal hyperplasia. The aims of our study were (1) to analyze the correlation between shear stress and release of transforming growth factor (TGF)-beta 1 by endothelial cells and (2) to determine the effect of TGF-beta 1 on smooth muscle cell proliferation

Oxidised LDL (OxLDL) induces production of platelet derived growth factor AA (PDGF AA) from aortic smooth muscle cells

Objectives: Elevated concentrations of oxidised low density lipoproteins (OxLDL) are associated with accelerated atherogenesis. The aim of our study was to determine the effect of OxLDL on the proliferation rate and platelet derived growth factor (PDGF) AA production on aortic smooth muscle cells. High density lipoproteins (HDL), which are known to have a protective effect against atherosclerosis, were used as control. Materials and methods: Bovine aortic smooth muscle cells were grown in presence of increased concentrations of OxLDL and HDL and in presence of control medium culture (DMEM). Proliferation rate was assessed by 3H-thymidine uptake. PDGF AA production was determined by ELISA and Western Blot Analysis. Results: OxLDL increased the proliferation rate of aortic smooth muscle cells as compared to DMEM and HDL (p < 0.001). The mitogenic activity of OxLDL on smooth muscle cells was reduced adding anti-PDGF AA antibodies (p < 0.001). PDGF AA production by aortic smooth muscle cells was increased after exposure to OxLDL as compared to DMEM (p < 0.001). HDL significantly reduced the production of PDGF AA by aortic smooth muscle cells (p < 0.001). Conclusions: Part of the atherogenic effect of OxLDL is mediated through the autocrine production of PDGF AA from aortic smooth muscle cells