Mineralocorticoid receptor-mediated signaling regulates the ion gated sodium channel in vascular endothelial cells and requires an intact cytoskeleton.
The PCR analysis followed by sequence alignment showed that both the mineralocorticoid receptor (MCR) and the epithelial sodium channel (ENaC) genes were expressed in the human vascular endothelial cell line (ECV). The growth and multiplication of the ECV in culture were influenced by both aldosterone and the MCR-specific antagonist ZK 91587. Following double labelled immunofluorescence recorded by confocal microscopy, both the MCR and the ENaC were found to colocalize with the tubulin filaments in ECV cells in situ; no association was observed with cellular actin. ZK 91587 not only eliminated the basal expression, but it also impaired the transactivation of the ENaC gene by aldosterone. The disruption of actin and tubulin by cytochalasin D and colchicine, respectively, resulted in the total elimination of ENaC induction by aldosterone. These studies suggest that (i) the transcriptional regulation of the ENaC gene by the MCR-mediated signalling is not restricted to epithelial cells and requires cytoskeleton integrity in ECV cells in situ, (ii) tubulin may form a new and novel mediator in cell regulation, and (iii) the vascular tone may actually be regulated via transactivation of the ion gated sodium channel in the endothelial cell of the blood vessels under direct, receptor-mediated action of aldosterone.
Golestaneh
N
N
Inserm E 9912, Centre Universitaire des Cordeliers, Paris, France.
Klein
C
C
Valamanesh
F
F
Suarez
G
G
Agarwal
M K
MK
Mirshahi
M
M
D000199:Actins / Q000032:analysis; D000450:Aldosterone / Q000494:pharmacology; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053503:Epithelial Sodium Channels; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014404:Tubulin / Q000032:analysis
D000199:Actins; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D014404:Tubulin; D015638:Cytochalasin D; D013148:Spironolactone; D000431:Ethanol; D000450:Aldosterone; C054537:ZK 91587