Search results for "PGC"
showing 10 items of 26 documents
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.
2020
Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin i…
Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer.
2020
Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signali…
Moderate exercise in mice improves cancer plus chemotherapy-induced muscle wasting and mitochondrial alterations
2019
Cancer cachexia is a multifactorial syndrome characterized by anorexia, body wasting, and muscle and adipose tissue loss, impairing patient's tolerance to anticancer treatments and survival. The aim of the present study was to compare the effects induced in mice by tumor growth alone (C26) or in combination with chemotherapy [C26 oxaliplatin and 5-fluorouracil (oxfu)] and to evaluate the potential of moderate exercise. Oxfu administration to C26 mice exacerbated muscle wasting and triggered autophagy or mitophagy, decreased protein synthesis, and induced mitochondrial alterations. Exercise in C26 oxfu mice counteracted the loss of muscle mass and strength, partially rescuing autophagy and m…
Skeletal muscle Heat shock protein 60 increases after endurance training and induces peroxisome proliferator-activated receptor gamma coactivator 1 α…
2016
AbstractHeat shock protein 60 (Hsp60) is a chaperone localizing in skeletal muscle mitochondria, whose role is poorly understood. In the present study, the levels of Hsp60 in fibres of the entire posterior group of hindlimb muscles (gastrocnemius, soleus and plantaris) were evaluated in mice after completing a 6-week endurance training program. The correlation between Hsp60 levels and the expression of four isoforms of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) were investigated only in soleus. Short-term overexpression of hsp60, achieved by in vitro plasmid transfection, was then performed to determine whether this chaperone could have a role in the activa…
Peroxisome proliferator-activated receptor-γ coactivator-1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mit…
2016
Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomi…
Long-Term Aspartame Administration Leads to Fibrosis, Inflammasome Activation, and Gluconeogenesis Impairment in the Liver of Mice
2021
Background: Aspartame is an artificial sweetener used in foods and beverages worldwide. However, it is linked to oxidative stress, inflammation, and liver damage through mechanisms that are not fully elucidated yet. This work aimed to investigate the effects of long-term administration of aspartame on the oxidative and inflammatory mechanisms associated with liver fibrosis progression in mice. Methods: Mice were divided into two groups with six animals each: control and aspartame. Aspartame (80 mg/kg, via oral) or vehicle was administrated for 12 weeks. Results: Aspartame caused liver damage and elevated serum transaminase levels. Aspartame also generated liver fibrosis, as evidenced by his…
Molecular basis of the effects of argan oil on mitochondrial and peroxisomal metabolism of the fatty acids and inflammation
2012
The objective of this thesis work was to explore the molecular basis of Argan Oil (AO) effects on the mitochondrial and peroxisomal lipid metabolism and to elucidate its anti-inflammatory potential. We thus showed, initially, that the artisanal method preparation preserved the antioxidant properties of AO preventing the oxidation of the ferulic acid, by contrast to AO of commercial origin. Then, the treatment by the AO or lipopolysaccharides (LPS) of human fibroblasts, the cellular model of pseudo-neonatal adrenoleukodystrophy (P-NALD), revealed for the AO that peroxisomes proliferation is independent from the activation of the nuclear receptor PPARα and the co-activator PGC-1α. On the othe…
Exercise and antioxidant supplements in the elderly
2013
Abstract Both exercise and aging increase reactive oxygen species (ROS), which can result in damage to cells. Aging is the result of damage caused by ROS to the mitochondrial genome in post mitotic cells and numerous studies have demonstrated an increase in ROS or their byproducts with exercise. ROS can cause oxidative stress as they overwhelm the antioxidant cellular defenses. Therefore interventions aimed at limiting or inhibiting ROS production, such as supplementation with antioxidant vitamins, should be able to reduce fatigue during muscle contraction and the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. However, it has been …
Fibroblast Growth Factor-21 (FGF-21) enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons.
2014
FGF-21 è un fattore di crescita ad azione endocrina principalmente espresso nel fegato con funzioni metaboliche; induce a livello epatico e in altri tessuti incremento di PGC1, ma le sue funzioni a livello cerebrale sono ancora sconosciute. PGC1 è espresso anche nel cervello dove mostra azione neuroprotettiva in neuroni dopaminergici in modelli animali di morbo di Parkinson. Scopo della ricerca era indagare possibili correlazioni tra le due proteine a livello cerebrale. I dati mostrano che FGF-21 induce attivazione di PGC1 mediante la deacetilasi Sirtuina-1 NAD+ dipendente, in neuroni dopaminergici e un incremento dell’attività respiratoria mitocondriale. FGF-21 risulta espresso nel cerv…
Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons via Sirtuin-1
2014
Abstract Mitochondrial dysfunctions accompany several neurodegenerative disorders and contribute to disease pathogenesis among others in Parkinson’s disease (PD). Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a major regulator of mitochondrial functions and biogenesis, and was suggested as a therapeutic target in PD. PGC-1α is regulated by both transcriptional and posttranslational events involving also the action of growth factors. Fibroblast growth factor-21 (FGF21) is a regulator of glucose and fatty acid metabolism in the body but little is known about its action in the brain. We show here that FGF21 increased the levels and activity of PGC-1α and elevated mito…