國家衛生研究院 NHRI:Item 3990099045/1268
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1268


    Title: Prostacyclin inhibits endothelial cell XIAP ubiquitination and degradation
    Authors: Liou, JY;Matijevic-Aleksic, N;Lee, S;Wu, KK
    Contributors: Center for Cardiovascular and Blood Research
    Abstract: To understand the role of prostacyclin (PGI(2)) in protecting endothelial cells from apoptosis, we evaluated the effects of carbaprostacyclin (cPGI(2)) on H2O2-induced human umbilical vein endothelial cell (HUVEC) apoptosis. cPGI(2) suppressed H2O2-induced annexin V-positive cells in a concentration- and time-dependent manner. Pre-treatment of HUVEC with 50 mu M cPGI(2) for 4 h produced the maximal antiapoptotic effect. Authentic PGI(2) generated by adenoviral transfer of PGI(2) synthetic genes exerted a similar protective effect. cPGI(2) inhibited Smac/DIABLO release from mitochondria, caspase 3 activation, focal adhesion protein degradation, and cell detachment. cPGI(2) selectively protected X-linked inhibitor of apoptosis protein (X-linked IAP, XIAP) from H2O2-induced ubiquitination, and preserved XIAP protein levels. PD-98059 but not H-89 abrogated the protective action of cPGI(2). cPGI(2) increased ERK phosphorylation which was blocked by PD-98059. HUVEC stably transfected with dominant negative Ras abrogated XIAP preservation by cPGI(2) while constitutive active Ras increased ERK phosphorylation and protected XIAP from degradation. Our results demonstrate for the first time that PGI(2) inhibits XIAP ubiquitination and degradation via the Ras/MEK-I/ERK signaling pathway. Preservation of XIAP proteins represents a key mechanism by which PGI(2) protects endothelial cells from oxidant-induced apoptosis. J. Cell. Physiol. 212: 840-848, 2007. (c) 2007 Wiley-Liss, Inc.
    Keywords: Cell Biology;Physiology
    Date: 2007-09
    Relation: Journal of Cellular Physiology. 2007 Sep;212(3):840-848.
    Link to: http://dx.doi.org/10.1002/jcp.21082
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0021-9541&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000248770500032
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34547940111
    Appears in Collections:[Kenneth Kun-Yu Wu] Periodical Articles

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