The effects of calcium channel blockers on nuclear factor kappa B activation in the mesangium cells

M. Hayashi, Y. Yamaji, Y. Nakazato, T. Saruta

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

It has been reported that calcium channel blockers (CCBs) have an inhibitory action on cell growth and transcriptional changes induced by cytokines and hormones. In this study, we examined the effects of CCBs on nuclear factor kappa B (NFκB), which plays a key role in the intracellular signaling of various growth factors and cytokines. The activity of NFκB was determined by luciferase assay with the transfection of the reporter gene, which has six NFκB-recognizing sequences in the upstream of herpes simplex virus thymidine kinase promoter. In cultured human mesangial cells, increased intracellular calcium concentration by calcium ionophore, A23187, showed a stimulatory effect on the phorbor 12-myristate 13-acetate (PMA)-induced activation of NFκB, while L-type calcium channel agonist, Bay K 8644, did not have any significant effects on either basal or PMA-stimulated activity of NFκB. At a higher concentration (10 μM), nifedipine, verapamil, or efonidipine showed an inhibitory effect on the activation of NFκB by PMA and A23187, while at a lower concentration (1 μM), only efonidipine showed a significant inhibitory effect. From these results, we conclude that CCBs have an inhibitory effect on NFκB via the independent pathway of an L-type calcium channel and that the potency of this effect is variable among L-type calcium channel blockers.

Original languageEnglish
Pages (from-to)521-525
Number of pages5
JournalHypertension Research
Volume23
Issue number5
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • Calcium channel blockers
  • Mesangium cells
  • Nuclear factor kappa B

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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