Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization

To identify the novel inhibitors of endoplasmic reticulumstress-induced cell death, we performed a high throughput assaywith a chemical library containing a total of 3280 bioactive smallmolecules. Cyclosporine A and bromocriptine were identified aspotent inhibitors of thapsigargiin-induced cell deat...

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Main Author: In Ki Kim1*, So Jung Park1, Jhang Ho Park1, Seung-Ho Lee2, Sung Eun Hong3 & John C. Reed3
Format: Article
Language:English
Published: Korean Society for Biochemistry and Molecular Biology 2012-08-01
Series:BMB Reports
Subjects:
Online Access:http://www.jbmb.or.kr/jbmb/pdf.php?data=MTMwMTIyMTdAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS04JTVEMTIwODMwMTcyMF8lMjg0ODItNDg3JTI5Qk1CXzEyLTAyNC5wZGY=
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author In Ki Kim1*, So Jung Park1, Jhang Ho Park1, Seung-Ho Lee2, Sung Eun Hong3 & John C. Reed3
author_facet In Ki Kim1*, So Jung Park1, Jhang Ho Park1, Seung-Ho Lee2, Sung Eun Hong3 & John C. Reed3
author_sort In Ki Kim1*, So Jung Park1, Jhang Ho Park1, Seung-Ho Lee2, Sung Eun Hong3 & John C. Reed3
collection DOAJ
description To identify the novel inhibitors of endoplasmic reticulumstress-induced cell death, we performed a high throughput assaywith a chemical library containing a total of 3280 bioactive smallmolecules. Cyclosporine A and bromocriptine were identified aspotent inhibitors of thapsigargiin-induced cell death (cut-off at4σ standard score) . However, U74389G, the potent inhibitor oflipid peroxidation had lower activity in inhibiting cell death. Theinhibition effect of cyclosporine A and bromocriptine wasspecific for only thapsigargin-induced cell death. The mechanismof inhibition by these compounds was identified as modificationof the expression of glucose regulated protein-78 (GRP-78/Bip)and inhibition of phosphorylation of p38 mitogen activatedprotein kinase (MAPK). However, these compounds did notinhibit the same events triggered by tunicamycin, which was inagreement with the cell survival data. We suggest that theinduction of protective unfolded protein response by thesecompounds confers resistance to cell death. In summary, weidentified compounds that may provide insights on cell deathmechanisms stimulated by ER stress.
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spelling doaj.art-d23d955230ee4a369881a197bd22873f2022-12-22T00:15:31ZengKorean Society for Biochemistry and Molecular BiologyBMB Reports1976-66961976-670X2012-08-01458482487Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilizationIn Ki Kim1*, So Jung Park1, Jhang Ho Park1, Seung-Ho Lee2, Sung Eun Hong3 & John C. Reed3To identify the novel inhibitors of endoplasmic reticulumstress-induced cell death, we performed a high throughput assaywith a chemical library containing a total of 3280 bioactive smallmolecules. Cyclosporine A and bromocriptine were identified aspotent inhibitors of thapsigargiin-induced cell death (cut-off at4σ standard score) . However, U74389G, the potent inhibitor oflipid peroxidation had lower activity in inhibiting cell death. Theinhibition effect of cyclosporine A and bromocriptine wasspecific for only thapsigargin-induced cell death. The mechanismof inhibition by these compounds was identified as modificationof the expression of glucose regulated protein-78 (GRP-78/Bip)and inhibition of phosphorylation of p38 mitogen activatedprotein kinase (MAPK). However, these compounds did notinhibit the same events triggered by tunicamycin, which was inagreement with the cell survival data. We suggest that theinduction of protective unfolded protein response by thesecompounds confers resistance to cell death. In summary, weidentified compounds that may provide insights on cell deathmechanisms stimulated by ER stress.http://www.jbmb.or.kr/jbmb/pdf.php?data=MTMwMTIyMTdAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS04JTVEMTIwODMwMTcyMF8lMjg0ODItNDg3JTI5Qk1CXzEyLTAyNC5wZGY=BromocriptineCalcium mobilizationCyclosporine AEndoplasmic reticulum stress
spellingShingle In Ki Kim1*, So Jung Park1, Jhang Ho Park1, Seung-Ho Lee2, Sung Eun Hong3 & John C. Reed3
Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization
BMB Reports
Bromocriptine
Calcium mobilization
Cyclosporine A
Endoplasmic reticulum stress
title Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization
title_full Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization
title_fullStr Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization
title_full_unstemmed Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization
title_short Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization
title_sort cyclosporine a and bromocriptine attenuate cell death mediated by intracellular calcium mobilization
topic Bromocriptine
Calcium mobilization
Cyclosporine A
Endoplasmic reticulum stress
url http://www.jbmb.or.kr/jbmb/pdf.php?data=MTMwMTIyMTdAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS04JTVEMTIwODMwMTcyMF8lMjg0ODItNDg3JTI5Qk1CXzEyLTAyNC5wZGY=
work_keys_str_mv AT inkikim1sojungpark1jhanghopark1seungholee2sungeunhong3johncreed3 cyclosporineaandbromocriptineattenuatecelldeathmediatedbyintracellularcalciummobilization