Showing papers by "Alessandra Stacchiotti published in 2014"
TL;DR: Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria-driven intrinsic apoptotic pathway, which possibly aid in reducing renal failure.
Abstract: Obesity is a common and complex health problem, which impacts crucial organs; it is also considered an independent risk factor for chronic kidney disease. Few studies have analyzed the consequence of obesity in the renal proximal convoluted tubules, which are the major tubules involved in reabsorptive processes. For optimal performance of the kidney, energy is primarily provided by mitochondria. Melatonin, an indoleamine and antioxidant, has been identified in mitochondria, and there is considerable evidence regarding its essential role in the prevention of oxidative mitochondrial damage. In this study we evaluated the mechanism(s) of mitochondrial alterations in an animal model of obesity (ob/ob mice) and describe the beneficial effects of melatonin treatment on mitochondrial morphology and dynamics as influenced by mitofusin-2 and the intrinsic apoptotic cascade. Melatonin dissolved in 1% ethanol was added to the drinking water from postnatal week 5–13; the calculated dose of melatonin intake was 100 mg/kg body weight/day. Compared to control mice, obesity-related morphological alterations were apparent in the proximal tubules which contained round mitochondria with irregular, short cristae and cells with elevated apoptotic index. Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria-driven intrinsic apoptotic pathway. These changes possibly aid in reducing renal failure. The melatonin-mediated changes indicate its potential protective use against renal morphological damage and dysfunction associated with obesity and metabolic disease.
49 citations
TL;DR: Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes, a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.
Abstract: Cisplatin (CisPt) is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h–8 h) before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.
22 citations
TL;DR: In this paper, the effect of high-potency statins on renal function is investigated, and it was shown that RVS-and Rvs plus EAAm-treated mice showed increased protein kinase B and endothelial nitric oxide synthase phosphorylation, but the target of rapamycin signaling pathway was not affected.
Abstract: The effects of high-potency statins on renal function are controversial. To address the impact of statins on renal morpho-functional aspects, normotensive young mice were treated with rosuvastatin (Rvs). Moreover, because statins may impair mitochondrial function, mice received either dietary supplementation with an amino acid mixture enriched in essential amino acids (EAAm), which we previously demonstrated to increase mitochondrial biogenesis in muscle or an unsupplemented control diet for 1 month. Mitochondrial biogenesis and function, apoptosis, and insulin signaling pathway events were studied, primarily in cortical proximal tubules. By electron microscopy analysis, mitochondria were more abundant and more heterogeneous in size, with dense granules in the inner matrix, in Rvs- and Rvs plus EAAm-treated animals. Rvs administration increased protein kinase B and endothelial nitric oxide synthase phosphorylation, but the mammalian target of rapamycin signaling pathway was not affected. Rvs increased the expression of sirtuin 1, peroxisome proliferator-activated receptor γ coactivator-1α, cytochrome oxidase type IV, cytochrome c, and mitochondrial biogenesis markers. Levels of glucose-regulated protein 75 (Grp75), B-cell lymphoma 2, and cyclin-dependent kinase inhibitor 1 were increased in cortical proximal tubules, and expression of the endoplasmic reticulum–mitochondrial chaperone Grp78 was decreased. EAAm supplementation maintained or enhanced these changes. Rvs promotes mitochondrial biogenesis, with a probable anti-apoptotic effect. EAAm boosts these processes and may contribute to the efficient control of cellular energetics and survival in the mouse kidney. This suggests that appropriate nutritional interventions may enhance the beneficial actions of Rvs, and could potentially prevent chronic renal side effects.
21 citations
TL;DR: Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria- driven intrinsic apoptotic pathway, which aid in reducing renal failure.
Abstract: Obesity is a common and complex health problem, which impacts crucial organs; it is also considered an independent risk factor for chronic kidney disease [1]. Few studies have analyzed the consequence of obesity in the renal proximal convoluted tubules, the major section of the reabsorptive process. To best perform its functions, the kidney requires energy primarily provided by mitochondria. Melatonin, indoleamine and antioxidant, has been identified in mitochondria, and overwhelming evidence has documented its essential role in the prevention of oxidative mitochondrial damage [2]. Herein, we evaluated the mechanism(s) of mitochondrial alterations in an animal model of obesity (ob/ob mice) and describe the beneficial effects of melatonin treatment on mitochondria morphology and dynamics as influenced by mitofusin- 2 and the intrinsic apoptotic cascade. Melatonin was dissolved in 1% ethanol and added to the drinking water from postnatal week 5 to 13; the calculated dose of melatonin intake was 100 mg/kg body weight/day. Compared to control mice, obesity-induced morphological alterations were apparent in the proximal tubules; the tubules contained round mitochondria with irregular, short cristae and the lining cells excited and elevated apoptotic index. Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria- driven intrinsic apoptotic pathway. The results aid in reducing renal failure. The melatonin-mediated changes probably suggest the use of melatonin to protect against renal morphological damage and dysfunction during metabolic disease.
TL;DR: The morphological analysis suggests that melatonin might ameliorate NAFLD by anti-oxidative and ER stress modulatory abilities in obese mice.
Abstract: Non alcoholic fatty liver disease (NAFLD) impacts on about 30% of the population in industrialized countries, associated to the metabolic syndrome may be reversible or dramatically evolve into cirrhosis or hepatocellular cancer (Wree et al., 2011). Leptin-deficient homozygous mice (ob/ob) represent a well-known animal model to study obesity, associated with overweight, liver steatosis and insulinresistance. Recently ER stress has been reported to contribute to hepatic steatosis and cell damage called lipoapoptosis (Flamment et al., 2010). Melatonin, the main pineal indoleamine, has been demonstrated to be useful to limit adipogenesis in many metabolic clinical conditions (de Luxan-Delgado et al., 2014). Therefore major aims of the present study were: 1.To localize ER stress, energy homeostasis and hypoxia markers in the liver of ob/ob mice receiving or not melatonin in drinking water at 100 mg/ kg/day for 8 weeks; 2.To characterize hepatic steatosis and quantify macrosteatosis in different experimental groups. C57BL6 mice treated or not with melatonin were used as controls. Remarkably in ob/ob mice receiving melatonin, macrosteatosis, periportal GRP78 staining decreased while beta catenin became basolateral into hepatocytes. Furthermore melatonin limited nuclear CHOP staining, a recognized index of major sensitivity to apoptosis, but stimulated p62/SQSTM1 signal, involved in reducing lipogenesis. Moreover by TEM analysis, we visualized in ob/ob mice liver mitochondria that displayed more cristae and strict RER adhesion after melatonin intake. In conclusion, our morphological analysis suggests that melatonin might ameliorate NAFLD by anti-oxidative and ER stress modulatory abilities in obese mice.