RESUMO
Klotho, a recently described gene, is mainly expressed in the kidney, and encodes a protein necessary for the activity of fibroblast growth factor receptors (FGFR), especially FGFR1. The Klotho protein has two variants, a transmembrane and a secreted form, and the latter may represent a new hormone synthesized by the kidney. Recent studies have shown that chronic kidney disease (CDK) is associated with significant alterations in the expression of klotho, and this alteration seems to be responsible for many of the phenotypic characteristics that accompany the uremic syndrome. CKD is associated with marked lymphocyte dysfunction, a clinically relevant problem, but the pathophysiological mechanisms behind this dysfunction are mostly unknown. Our research group has recently demonstrated the expression of klotho andFGFR1 in human lymphocytes and is currently implementing a series of experiments designed to determine the role of this pathway in the pathogenesis of lymphocyte dysfunction associated with uremia.
Assuntos
Animais , Envelhecimento/imunologia , Fenótipo , Camundongos/classificação , Camundongos/crescimento & desenvolvimento , Insuficiência Renal/fisiopatologiaRESUMO
Liquid chromatography coupled to tandem mass spectrometry has been used for the detection and the structural characterization of T-rich model oligonucleotides covalently modified by estradiol-2,3-quinone. After separation by gradient elution, adducts were analyzed by negative electrospray mass spectrometry, enabling to evidence and localize the modifications in the oligonucleotide sequence. Modifications by one molecule of estrogen were evidenced on purines (A, G) whereas no reaction was observed on pyrimidic bases (T). Isomeric adducts were differentiated using tandem mass spectrometry, and energy resolved mass spectrometry allowed to underline differences in the behavior of the adducts towards collisional excitation into an ion trap device.