Repressed Ca2+ clearance in parthenolide-treated murine brain bEND.3 endothelial cells

Tien Yao Tsai, Shyh Liang Lou, Ka Shun Cheng, Kar Lok Wong, Mei Ling Wang, Tzu Hui Su, Paul Chan, Yuk Man Leung

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Abstract

Parthenolide is a sesquiterpene lactone compound isolated from the leaves and flowerheads of the plant feverfew (Tanacetum parthenium). The anticancer effects of parthenolide have been well studied and this lactone compound is currently under clinical trials. Parthenolide is also a protective agent in cardiac reperfusion injury via its inhibition of nuclear factor-κB (NF-κB). Not much is known if this compound affects signal transduction in non-tumor cells. We investigated whether parthenolide affected Ca2+ signaling in endothelial cells, key components in regulating the vascular tone. In this work using mouse cortical microvascular bEND.3 endothelial cells, we found that a 15-h treatment with parthenolide resulted in amplified ATP-triggered Ca2+ signal; the latter had a very slow decay rate suggesting suppression of Ca2+ clearance. Evidence suggests parthenolide suppressed Ca2+ clearance by inhibiting the plasmalemmal Ca2+ pump; such suppression did not result from decreased expression of the plasmalemmal Ca2+ pump protein. Rather, such suppression was possibly a consequence of endoplasmic reticulum (ER) stress, since salubrinal (an ER stress protector) was able to alleviate parthenolide-induced Ca2+ clearance suppression. Given the current deployment of parthenolide as an anti-cancer drug in clinical trials and the potential usage of this lactone as a cardioprotectant, it is important to examine in details the perturbing effects of parthenolide on Ca2+ homeostasis in endothelial cells and neighboring vascular smooth muscle cells, activities of which exert profound effects on hemodynamics.

Original languageEnglish
Pages (from-to)280-286
Number of pages7
JournalEuropean Journal of Pharmacology
Volume769
DOIs
Publication statusPublished - Dec 15 2015

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Keywords

  • Ca clearance
  • Ca pump
  • Endoplasmic reticulum stress
  • Endothelial cells
  • Parthenolide

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tsai, T. Y., Lou, S. L., Cheng, K. S., Wong, K. L., Wang, M. L., Su, T. H., Chan, P., & Leung, Y. M. (2015). Repressed Ca2+ clearance in parthenolide-treated murine brain bEND.3 endothelial cells. European Journal of Pharmacology, 769, 280-286. https://doi.org/10.1016/j.ejphar.2015.11.031