Regulation of Preproendothelin-1 Transcripts by Lysophosphatidic Acid in Rat Endothelial Cells
Document Type
Article
Publication Date
12-1-1997
Description
Lysophosphatidic acid (LPA) is a platelet-derived phospholipid which has been shown to cause immediate hypertension in rats. The following experiments were designed to assess the involvement of endothelin-1 (ET-1) in LPA-induced hypertension. LPA was found to upregulate preproET-1 transcripts in endothelial cells which were derived from rat hearts and aortae in a dose and time-dependent manner. PreproET-1 mRNA level was elevated within 15 min and maximal induction was achieved by 30 min after the addition of 0.5 μM LPA. Cycloheximide superinduced the preproET-1 mRNA level and actinomycin D abolished the induction. In addition, the induction could be blocked by H7, an inhibitor of protein kinase C. These findings indicate that the induction of preproET-1 transcripts by LPA involves the activation of protein kinase C and de novo RNA synthesis. Since ET-1 is a very potent vasoconstrictor with long lasting effect, the increase in ET-1 production may serve to amplify and augment the effect of LPA on hypertension.
Citation Information
Chua, C. C.; Chua, B. H.L.; and Hamdy, R. C.. 1997. Regulation of Preproendothelin-1 Transcripts by Lysophosphatidic Acid in Rat Endothelial Cells. FASEB Journal. Vol.11(3). ISSN: 0892-6638