RESUMO
In human bone marrow endothelial cell (HBMEC) exposed for 8 h to aldosterone, the microarray screening revealed an upregulation of the mRNAs for six genes and downregulation of mRNAs for four genes, all implicated in hemostasis. In HBMEC, immunocytochemistry revealed the presence of the membrane-bound endothelial protein C receptor (EPCR) whereas the mineralocorticoid receptor (MCR) was present as a nucleo-cytoplasmic. In HBMEC treated with aldosterone the induction of EPCR protein was evident by both FACS analysis and dot blot procedure. When aldosterone-treated HBMEC were incubated with the activated protein C (APC), the partial thromboplastin clotting time (aPTT) increased 2.5-fold over control, from 10 to 25 s. The MCR antagonists aldactone and eplerenone reduced the basal coagulation time in untreated cells to 33.5% and 42% of the control, respectively. These data add an entirely new dimension to delineating the receptor-mediated action of mineralocorticoid hormones.
Assuntos
Aldosterona/fisiologia , Antígenos CD/genética , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Hemostasia/genética , Receptores de Superfície Celular/genética , Aldosterona/farmacologia , Antígenos CD/biossíntese , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , Membrana Celular/metabolismo , Células Cultivadas , Citoplasma/metabolismo , Receptor de Proteína C Endotelial , Endotélio Vascular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Hemostasia/efeitos dos fármacos , Humanos , Tempo de Tromboplastina Parcial , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/agonistas , Receptores de Superfície Celular/biossíntese , Receptores de Mineralocorticoides/genética , Receptores de Mineralocorticoides/metabolismo , Regulação para CimaRESUMO
Sodium-water balance is causally linked to the functional expression of a number of important ocular tissues, viz. corneal deturgescence, aqueous humor secretion by the iris, hydration of the lens, retinal photoreception, and choriocapillary angiogenesis. The regulation of sodium absorption in the eye is generally believed to be under the control of Na(+),K(+)-activated adenosine triphosphatase, although evidence for this view is at best circumstantial. Contemporary work has shown widespread distribution of the mineralocorticoid hormone receptor and its colocalization with the amiloride-sensitive sodium channel in cells of diverse embryological origins. All available evidence favors the idea that the transcriptional regulation of the apical sodium channel by adrenocorticoids, and not the basolateral sodium pump, is critically important to sodium-water homeostasis in various ocular tissues, in a manner previously believed to be limited exclusively to the epithelial cell in various peripheral organs. Based upon these parameters, models are presented to help in understanding the direction of sodium absorption in a number of ocular tissues. Thus, the regulation of the sodium channel by steroid hormones seems to be a universal feature of the living cell that may have important implications in the understanding and management of normal ocular functions and their modification in human pathology.
