ABSTRACT
The nuclear receptor PPARs (peroxisomal proliferators-activated receptors) are transcription factors activated by natural and synthetic ligands. Three different isoforms of PPARs have been described, PPARalpha, PPARbeta/ delta, and PPARgamma. PPARs isoforms are tissue-dependent expressed and they regulate the gene expression of proteins involved in glucose and lipid metabolism. Selective pharmacological activation of these isoforms has revealed their role in cellular physiology. Nowadays, two kinds of PPARs agonists are currently used in the clinical practice, the fibrate hypolipidemic drugs, used in the treatment of dyslipidemia, are synthetic ligands for PPARalpha, whereas thiazolidinediones or glitazones have PPARgamma selectivity and are used as hypoglycemic agents. The main cellular effect of PPAR activation lies on fatty acid oxidation and mobilization (PPARalpha) as well as they act as insulin sensitizers on peripheral tissues (PPARgamma). In addition to these beneficial effects of PPARs, it has also been demonstrated that PPARs activation can prevent cardiac dysfunction in diabetic patients as well as the anti-inflammatory processes developed in many diseases. Recent development of PPARbeta/delta and hybrid PPARs alpha and gamma agonists, and their clinical trials are giving promising outcomes in the therapeutics of metabolic syndrome, diabetes and cardiac diseases.
Subject(s)
Animals , Humans , Heart Diseases , Metabolic Syndrome , Peroxisome Proliferator-Activated Receptors/physiology , Insulin Resistance , Metabolic Syndrome , Myocardium , Peroxisome Proliferator-Activated ReceptorsABSTRACT
Tumor cells show several modifications in their metabolism in comparison with normal cells. In particular, tumor cells show an accelerated glycolysis and a low O2 dependence, which are matabolic modifications involved in the resistance of many tumor cell lines to radiation. Thus, a strategy to enhace the radiosensitivity could be the transformation of the glycolytic metabolism of tumor cells into an oxidative type of metabolism, i.e., to induce the ATP supply to dependend solely on oxidative phosphorylation. Therefore, this review emphasizes the relevance of oxidative phosphorylation on tumor cells regarding (a) its contributions to ATP supply for cell duplication during the proliferative phase, and (b) the possible therapeutic implications of having oxidative rather than glycolytic tumor cells
Subject(s)
Humans , Animals , Cell Division/physiology , Glycolysis/physiology , Oxidative Phosphorylation , Time Factors , Tumor Cells, CulturedABSTRACT
En los últimos años de ha acumulado evidencia que indica un posible daño posterior a la reperfusión miocárdica; sin embargo, no se sabe exactamente si la reperfusión por sí misma es la que produce el daño o acelera el daño producido a las células durante la isquemia. Se han asociado algunas patologías al daño por reperfusión como la aparición de arritmias, el miocardio aturdido y el daño vascular con ausencia de reflujo. En esta revisión se discuten las principales hipótesis que explican los mecanismos del daño inducido por la reperfusión miocárdica como son la sobrecarga de calcio, el daño causado por los radicales libres y otros. También se describen los modelos experimentales usados comúnmente y los fármacos que se han utilizado en los últimos años para tratar de disminuir la intensidad de este fenómeno