{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:13:51Z","timestamp":1790943231345,"version":"4.1.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:p> Pigment epithelium-derived factor (PEDF) is an intrinsic antiangiogenic factor and a potential therapeutic agent. Previously, we discovered the mechanism of PEDF-induced apoptosis of human umbilical vein endothelial cells (HUVECs) as sequential induction\/activation of p38 mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor gamma (PPAR-\u03b3), and p53. In the present study, we investigated the signaling role of cytosolic calcium-dependent phospholipase A<jats:sub>2<\/jats:sub>-\u03b1 (cPLA<jats:sub>2<\/jats:sub>-\u03b1) to bridge p38 MAPK and PPAR-\u03b3 activation. PEDF induced cPLA<jats:sub>2<\/jats:sub>-\u03b1 activation in HUVECs and in endothelial cells in chemical burn-induced vessels on mouse cornea. The cPLA<jats:sub>2<\/jats:sub>-\u03b1 activation is evident from the phosphorylation and nuclear translocation of cPLA<jats:sub>2<\/jats:sub>-\u03b1 as well as arachidonic acid release and the cleavage of PED6, a synthetic PLA<jats:sub>2<\/jats:sub> substrate. Such activation can be abolished by p38 MAPK inhibitor. The PEDF-induced PPAR-\u03b3 activation, p53 expression, caspase-3 activity, and apoptosis can be abolished by both cPLA<jats:sub>2<\/jats:sub> inhibitor and small interfering RNA targeting cPLA<jats:sub>2<\/jats:sub>-\u03b1. Our observation not only establishes the signaling role of cPLA<jats:sub>2<\/jats:sub>-\u03b1 but also for the first time demonstrates the sequential activation of p38 MAPK, cPLA<jats:sub>2<\/jats:sub>-\u03b1, PPAR-\u03b3, and p53 as the mechanism of PEDF-induced endothelial cell apoptosis. <\/jats:p>","DOI":"10.1152\/ajpcell.00432.2008","type":"journal-article","created":{"date-parts":[[2008,12,18]],"date-time":"2008-12-18T16:03:35Z","timestamp":1229616215000},"page":"C273-C284","source":"Crossref","is-referenced-by-count":25,"title":["Cytosolic phospholipase A<sub>2<\/sub>-\u03b1 is an early apoptotic activator in PEDF-induced endothelial cell apoptosis"],"prefix":"10.1152","volume":"296","author":[{"given":"Tsung-Chuan","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Show-Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuh-Cheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hsiu","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Wen","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Chuan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeou-Ping","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Ambati BK, Anand A, Joussen AM, Kuziel WA, Adamis AP, Ambati J. 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