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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Format: | Article |
Language: | English |
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Korean Society for Biochemistry and Molecular Biology
2012-08-01
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Series: | BMB Reports |
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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. |
first_indexed | 2024-12-12T18:46:36Z |
format | Article |
id | doaj.art-d23d955230ee4a369881a197bd22873f |
institution | Directory Open Access Journal |
issn | 1976-6696 1976-670X |
language | English |
last_indexed | 2024-12-12T18:46:36Z |
publishDate | 2012-08-01 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | Article |
series | BMB Reports |
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 |