RESUMO
Preeclampsia (preE) is a hypertensive disorder of pregnancy. Cardiotonic steroids (CTS) are endogenous inhibitors of Na+/K+ ATPase, and at least one CTS, marinobufagenin (MBG), is elevated in a rat model of preE prior to the development of the syndrome. MBG and ouabain impair cytotrophoblast (CTB) cell function, which is critical for placental development. We evaluated the effect of a CTS, cinobufotalin (CINO), on CTB cell function in vitro. CINO at ≥1 nM inhibited CTB cell proliferation, migration, and invasion (p < 0.05), but had no effect on cell viability. There was a higher (p < 0.05) percentage of G0/G1 phase cells in groups treated with CINO at ≥1 nM. CINO caused an increase in stress signaling p38 MAPK and a positive annexin-V staining in CTB cells, indicating the activation of apoptotic signaling. However, the CINO-induced apoptotic signaling was prevented by p38 inhibition. These data demonstrate that CINO impairs CTB cell function via cell cycle arrest and apoptotic signaling.
Assuntos
Apoptose/efeitos dos fármacos , Bufanolídeos/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Trofoblastos/metabolismo , Animais , Linhagem Celular , Feminino , Humanos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Ratos , Trofoblastos/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Renin is the rate limiting enzyme in the renin-angiotensin (RA) system that regulates blood pressure and electrolyte balance. In this study, we investigated the renin inhibitory effect of a royal jelly (RJ)-derived peptide. A dipeptide YY was isolated from the digested fraction of RJ proteins by proteases and was found to inhibit human renin activity. The inhibition constant (Ki) of YY was estimated to be 10 microM when the Km was 0.16 microM using sheep angiotensinogen as the substrate. The peptide was observed to lower blood pressure in spontaneously hypertensive rats.
