RESUMO
Autosomal-dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder characterized by abnormal proliferation of renal tubular epithelium, leading to massive kidney enlargement and progressive chronic kidney disease. ADPKD is caused by mutations in PKD1 and PKD2 genes. Herein, we describe and characterize a novel missense mutation in the PKD2 gene (c.1320G>T) in a 41-year-old White man with kidney cysts and a family history of ADPKD. This mutation abolishes a conserved acceptor splice site of intron 5, resulting in a premature termination following the addition of three aberrant amino acids (PKD2 p.L441C fsX4). We demonstrate that the aberrantly spliced transcript is found in substantial amounts in the patient's peripheral blood leukocytes (PBL), and show that this alternative splicing of exon 6 occurs, to a lesser magnitude, in other patients with ADPKD and in normal control individuals. The biological and clinical significance of this splice variant in ADPKD is currently unknown.
Assuntos
Cistos/genética , Falência Renal Crônica/genética , Rim/patologia , Mutação de Sentido Incorreto , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Adulto , Cistos/patologia , Análise Mutacional de DNA , Éxons , Humanos , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/etiologia , Masculino , Dados de Sequência Molecular , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Sítios de Splice de RNA , Splicing de RNA , Canais de Cátion TRPP/metabolismo , UltrassonografiaRESUMO
The cardioprotective properties of pharmacological and metabolic activators of mitoKATP are reviewed. Metabolic activators of the channels and data on their cardioprotective properties are discussed in the review. The authors adduce their own data concerning cardioprotective properties of mitoKATP channel metabolic activator (UDP). In experimental animals, UDP precursors, uridine and UMP, decrease myocardial ischemic alteration index and T-wave amplitude within 60 min after occlusion of the left coronary artery. Both effects are prevented by mitoKATP channel inhibitors, glibenclamide and 5-HD. UMP and uridine possess antiarrhythmic properties as well. These preparations decrease the number of premature ventricular beats, the duration of ventricular tachycardia and fibrillation, and these effects are eliminated mainly by glibenclamide. Thus, mitoKATP plays a significant role in prevention of both ischemic lesions and rhythm disorders. The prospects of application of metabolic activators to prevent and treat myocardial infarction are discussed.
