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Vascular pharmacology

Protein kinase C-δ (PKC-δ) and PKC-α mediate Ca(2+)-dependent increases in CNP mRNA in human vascular cells.


PMID 22583821

Abstract

C type natriuretic peptide (CNP) functions as a paracrine/autocrine vasoprotectant. CNP mRNA is up-regulated in human vascular smooth muscle cells (SMC) by PDGF-BB via a protein kinase C (PKC)-dependent pathways, and by general PKC activation with phorbol myristate acetate (PMA). In this report we examine the calcium dependence and isotype specificity of these PKC/CNP pathways. The PKC-δ-specific inhibitor rottlerin blocked the increase in CNP mRNA and immunoreactive CNP following treatment of aortic SMC (AoSMC) with PDGF-BB. A 300-400-fold PMA-induced elevation of CNP transcript levels in AoSMC and a ~40-fold increase in human aortic endothelial cells (HAEC) were reduced by PKC-α- and PKC-δ-, but not PKC-β-specific inhibitors. siRNA silencing of PKC-δ reduced PDGF-, but not PMA-stimulated CNP transcript in SMC. Inhibition of intracellular Ca(2+) mobilization abolished a PMA-stimulated increase in CNP transcript in both SMC and HAEC. The results of this study show that PDGF increases CNP in SMC via a protein kinase C-δ-dependent pathway. In contrast, PMA increases CNP expression using PKC-α- and PKC-δ-pathways in both SMC and HAEC. A 8-10-fold greater PMA-induced increase in CNP transcript in SMC than in HAEC suggests that smooth muscle cells could be selectively targeted for CNP up-regulation by PKC-α- and PKC-δ-activators.

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R5648
Rottlerin
C30H28O8