Document Detail

Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization.
MedLine Citation:
PMID:  22917034     Owner:  NLM     Status:  In-Data-Review    
To identify the novel inhibitors of endoplasmic reticulum stress-induced cell death, we performed a high throughput assay with a chemical library containing a total of 3280 bioactive small molecules. Cyclosporine A and bromocriptine were identified as potent inhibitors of thapsigargiin-induced cell death (cut-off at 4σ standard score) . However, U74389G, the potent inhibitor of lipid peroxidation had lower activity in inhibiting cell death. The inhibition effect of cyclosporine A and bromocriptine was specific for only thapsigargin-induced cell death. The mechanism of inhibition by these compounds was identified as modification of the expression of glucose regulated protein-78 (GRP-78/Bip) and inhibition of phosphorylation of p38 mitogen activated protein kinase (MAPK). However, these compounds did not inhibit the same events triggered by tunicamycin, which was in agreement with the cell survival data. We suggest that the induction of protective unfolded protein response by these compounds confers resistance to cell death. In summary, we identified compounds that may provide insights on cell death mechanisms stimulated by ER stress. [BMB Reports 2012; 45(8): 482-487].
In Ki Kim; So Jung Park; Jhang Ho Park; Seung-Ho Lee; Sung Eun Hong; John C Reed
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  BMB reports     Volume:  45     ISSN:  1976-670X     ISO Abbreviation:  BMB Rep     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101465334     Medline TA:  BMB Rep     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  482-7     Citation Subset:  IM    
Asan Institute for Life Science, Asan Medical Center, Seoul 138-736, Korea
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