Research

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Interleukin-1beta regulates the human brain natriuretic peptide promoter via Ca(2+)-dependent protein kinase pathways.

Q He; M C LaPointe (Profiled Author: Margot C LaPointe)

Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI 48202-2689, USA.
Hypertension 2000;35(1 Pt 2):292-6.

We have shown that interleukin-1beta (IL-1beta) activates the human brain natriuretic peptide (hBNP) promoter via a transcriptional mechanism. Others have reported that changes in intracellular calcium (Ca(2+)) mediate the action of IL-1beta. We questioned whether Ca(2+) and Ca(2+)-dependent pathways mediate IL-1beta regulation of the hBNP promoter in cardiac myocytes. The hBNP promoter (-1818 to +100) coupled to a luciferase cDNA reporter gene was transferred into neonatal cardiac myocytes. Cells were then treated with agents that modify Ca(2+) levels or inhibit Ca(2+)-dependent kinases, and luciferase activity was measured as an index of hBNP promoter activity. The Ca(2+) ionophore A23187 increased hBNP promoter activity; however, neither EGTA nor nifedipine reduced IL-1beta-stimulated promoter activity. Long-term treatment with thapsigargin, which depletes intracellular Ca(2+) stores, decreased basal promoter activity and blocked the effect of IL-1beta. Inhibition of protein kinase C completely blocked IL-1beta-stimulated hBNP promoter activity, whereas inhibition of Ca(2+)/calmodulin-dependent kinase II decreased promoter activity by 40%. In contrast, inhibition of the Ca(2+)-regulated phosphatase calcineurin by cyclosporin A had no effect. These data suggest that (1) Ca(2+) activates the hBNP promoter; (2) release of Ca(2+) from intracellular stores is important to IL-1beta regulation of the hBNP promoter, but transport via voltage-sensitive Ca(2+) channels is not; (3) protein kinase C and Ca(2+)/calmodulin-dependent kinase II mediate the action of IL-1beta; and (4) the phosphatase calcineurin is not involved in IL-1beta regulation of the hBNP promoter. Thus, Ca(2+) and Ca(2+)-dependent pathways are critical to IL-1beta regulation of the hBNP promoter.

2 Originating Grant

• 1.

  CARRETERO, OSCAR A.

  Autocoids in Hypertension: Pathogenesis and End Organ Damage

  1 September 1982 - 31 January 2018

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

  Total Funding: $ 51,980,043

• 2.

  Lapointe, Margot C

  REGULATION OF ANF AND BNP IN CARDIAC HYPERTROPHY

  Total Funding: $ 318,330

Scientific Context

This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.