R. Corder et S. Barker, The expression of endothelin-1 and endothelin-converting enzyme-1 (ECE-1) are independently regulated in bovine aortic endothelial cells, J CARDIO PH, 33(4), 1999, pp. 671-677
Citations number
44
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
The endopeptidase called endothelin-converting enzyme-1 (ECE-1) is thought
to play a physiological role in endothelin-l (ET-1) biosynthesis. For human
ECE-1, differential splicing of messenger RNA (mRNA) results in the synthe
sis of three isoforms, termed ECE-1a, ECE-1b, and ECE-1c. The isoform(s) re
sponsible for the hydrolysis of the biosynthetic intermediate big ET-1 in e
ndothelial cells have yet to be assigned. To investigate whether the expres
sion of mRNAs for preproET-1 and ECE-1 are regulated in parallel, a variety
of conditions were used to compare levels of ET-1 synthesis by bovine aort
ic endothelial cells (BAECs) with levels of mRNA for preproET-1, ECE-la, EC
E-lc, and the combined ECE-1 isoforms (ECE-1a/b/c), Stimulation of BAECs wi
th tumor necrosis factor-alpha or transforming growth factor-beta increased
ET-1 synthesis, and treatment of BAECs with 2-chloroadenosine or staurospo
rine caused concentration-dependent reductions in ET-1 synthesis. Estimates
of mRNA levels by reverse transcription-polymerase chain reaction (RT-PCR)
with linear cycling conditions showed changes in preproET-1 expression to
correlate well with ET-I secretion. In contrast, RT-PCR analysis of ECE-1 e
xpression by using primer pairs to measure ECE-la, ECE-lc, or all the ECE-1
isoforms simultaneously showed no correlation between their mRNA levels an
d those of preproET-1. This indicates that under the conditions investigate
d, expression of ECE-1 is not coordinated with ET-1 synthesis in BAECs.