Transcriptional Activation of Low Density Lipoprotein Receptor Gene by Angiotensin-Converting Enzyme Inhibitors and Ca2+-Channel Blockers Involves Protein Kinase C Isoforms
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Medientyp:
E-Artikel
Titel:
Transcriptional Activation of Low Density Lipoprotein Receptor Gene by Angiotensin-Converting Enzyme Inhibitors and Ca2+-Channel Blockers Involves Protein Kinase C Isoforms
Erschienen:
National Academy of Sciences of the United States of America, 1993
Erschienen in:Proceedings of the National Academy of Sciences of the United States of America
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>The pharmacological potency of angiotensin-converting enzyme (ACE) inhibitors (lisinopril and enalaprilat) on the transcription of low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase genes was examined in human vascular smooth muscle cells and compared with the action of Ca<sup>2+</sup>-channel blockers (manidipine, verapamil, and diltiazem). Analogous to Ca<sup>2+</sup>-channel blockers, nanomolar concentrations of enalaprilat or lisinopril stimulated the synthesis of low density lipoprotein receptor mRNA and amplified the transcription induced by recombinant platelet-derived growth factor BB. In contrast to Ca<sup>2+</sup>-channel blockers, ACE inhibitors did not alter the transcription of the 3-hydroxy-3-methylglutaryl-CoA reductase gene. Platelet-derived growth factor BB stimulated the translocation of ∂ and ε isoforms of protein kinase C. Similar to Ca<sup>2+</sup>-channel blockers, ACE inhibitors reduced the translocation of ∂ and ε isoforms of protein kinase C. Furthermore, ACE inhibitors and Ca<sup>2+</sup>-channel blockers inhibited platelet-derived growth factor BB-induced transcription of c-fos and c-jun genes. The findings suggest that increased de novo synthesis of mRNA low density lipoprotein receptor apparently involves the participation of =partial and ε isoforms of protein kinase C and transcription factors c-Fos and c-Jun.</p>