國家衛生研究院 NHRI:Item 3990099045/3280
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3280


    Title: Nonsteroidal anti-inflammatory drugs induced endothelial apoptosis by perturbing peroxisome proliferator-activated receptor-delta transcriptional pathway
    Authors: Liou, JY;Wu, CC;Chen, BR;Yen, LB;Wu, KK
    Contributors: Institute of Cellular and Systems Medicine
    Abstract: Recent studies have shown that use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of myocardial infarction. To explore whether NSAIDs may induce endothelial apoptosis and thereby enhance atherothrombosis, we treated human umbilical vein endothelial cells (HUVECs) with sulindac sulfide (SUL), indomethacin (IND), aspirin (ASA), or sodium salicylate (NaS), and we analyzed apoptosis. SUL and/or IND significantly increased annexin V-positive cells, cleaved poly(ADP-ribose) polymerase (PARP) and caspase-3. ASA and NaS at 1 mM did not induce PARP cleavage or caspase-3 and at 5 mM, ASA but not NaS increased apoptosis. Because peroxisome proliferator-activated receptor δ-mediated 14-3-3ε up-regulation was reported to play a crucial role in protecting against apoptosis, we determined whether NSAIDs suppress this transcriptional pathway. SUL, IND, and ASA (5 mM) suppressed PPARδ and 14-3-3 proteins in a manner parallel to PARP cleavage. Neither ASA nor NaS at 1 mM interfered with PPARδ or 14-3-3ε expression. SUL inhibited PPARδ promoter activity, which correlated with 14-3-3ε promoter suppression. Suppression of 14-3-3ε was associated with increased Bad translocation to mitochondria. Neither carbaprostacylin nor 4-(3-(2-propyl-3-hydroxy-4-acetyl)-phenoxy)propyloxyphenoxy acetic acid (L-165041) prevented HUVECs from SUL-induced apoptosis. Because of suppression of ectopic PPARδ by sulindac, adenoviral PPARδ transduction failed to restore 14-3-3ε or prevent PPAR cleavage. Our findings suggest that NSAIDs, but not aspirin (<1 mM) induce endothelial apoptosis via suppression of PPARδ-mediated 14-3-3ε expression.
    Date: 2008-11
    Relation: Molecular Pharmacology. 2008 Nov;74(5):1399-1406.
    Link to: http://dx.doi.org/10.1124/mol.108.049569
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0026-895X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000260197300023
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=54349108364
    Appears in Collections:[Kenneth Kun-Yu Wu] Periodical Articles
    [Jun-Yang Liou] Periodical Articles
    [Betty Lin-Ju Yen] Periodical Articles

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