RESUMO
In the brush border of intestinal and kidney epithelial cells, scaffolding proteins ezrin, Na(+)-H(+) exchanger regulatory factor (NHERF)1 and NHERF2 play important roles in linking transmembrane proteins to the cytoskeleton and assembling signalling regulatory complexes. The last 30 carboxyl residues of NHERF1 and NHERF2 form the EBDs [ezrin, radixin and moesin (ERM)-binding domain]. The current study found that NHERF1/2 contain an ERM-binding regulatory sequence (EBRS), which facilitates the interaction between the EBD and ezrin. The EBRSs are located within 24 and 19 residues immediately upstream of EBDs for NHERF1 and NHERF2 respectively. In OK (opossum kidney) epithelial cells, EBRSs are necessary along with the EBD to distribute NHERF1 and NHERF2 exclusively to the apical domain. Furthermore, phosphorylation of Ser(303) located in the EBRS of NHERF2, decreases the binding affinity for ezrin, dislocates apical NHERF2 into the cytosol and increases the NHERF2 microvillar mobility rate. Moreover, increased phosphorylation of Ser(303) was functionally significant preventing acute stimulation of NHE3 (Na(+)-H(+) exchanger 3) activity by dexamethasone.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Dexametasona/farmacologia , Fosfoproteínas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Células CACO-2 , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Dados de Sequência Molecular , Gambás , Fosfoproteínas/genética , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/genética , Fatores de Transcrição/genéticaRESUMO
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new type of oral hypoglycaemic agent with good cardiovascular protective effects. There are several lines of clinical evidence suggest that SGLT2i can significantly reduce the risks of heart failure, cardiovascular death, and delay the progression of chronic kidney disease. In addition, recent basic and clinical studies have also reported that SGLT2i also has good anti-arrhythmic effects. However, the exact mechanism is poorly understood. The aim of this review is to summarize recent clinical findings, studies of laboratory animals, and related study about this aspect of the antiarrhythmic effects of SGLT2i, to further explore its underlying mechanisms, safety, and prospects for clinical applications of it.