title: Repressed Ca(2+) clearance in parthenolide-treated murine brain bEND.3 endothelial cells.
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 Ca(2+) 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 Ca(2+) signal; the latter had a very slow decay rate suggesting suppression of Ca(2+) clearance. Evidence suggests parthenolide suppressed Ca(2+) clearance by inhibiting the plasmalemmal Ca(2+) pump; such suppression did not result from decreased expression of the plasmalemmal Ca(2+) 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 Ca(2+) 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 Ca(2+) homeostasis in endothelial cells and neighboring vascular smooth muscle cells, activities of which exert profound effects on hemodynamics.
authors.affiliation: Cardiovascular Division, Lotung Poh-Ai Hospital, Luodong, Taiwan; Department of Biomedical Engineering, Chung Yuan Christian University, Chungli, Taiwan.
authors.forename: Tien-Yao
authors.initials: TY
authors.lastname: Tsai
authors.affiliation: Department of Biomedical Engineering, Chung Yuan Christian University, Chungli, Taiwan.
authors.forename: Shyh-Liang
authors.initials: SL
authors.lastname: Lou
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ka-Shun
authors.initials: KS
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Kar-Lok
authors.initials: KL
authors.lastname: Wong
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Tzu-Hui
authors.initials: TH
authors.lastname: Su
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan. Electronic address: ymleung@mail.cmu.edu.tw.
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D051379:Mice; D055806:Microvessels / Q000166:cytology; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D012717:Sesquiterpenes; C002669:parthenolide; D002118:Calcium
keywords: Ca(2+) clearance; Ca(2+) pump; Endoplasmic reticulum stress; Endothelial cells; Parthenolide