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New apoptosis gene therapy research from Mackay Memorial Hospital discussed
December 10th, 2007
2007 DEC 10 -- Research findings, 'PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells,' are discussed in a new report. According to recent research published in the journal Cardiovascular Research, "Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. The pathway mediating endothelial cell apoptosis has not been fully established." "Here we investigated the participation of peroxisome proliferator-activated receptor gamma (PPARgamma) and p53 in the apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs pretreated with either PPARgamma antagonist or PPARgamma small interfering RNA (siRNA) suppressed PEDF-induced apoptosis as determined by TUNEL assay, annexin V-FITC/PI staining, and cleavage of procaspase-8, -9, -3. PEDF sequentially induced PPARgamma and p53 expression as observed in immunoblotting and immunofluoresence assays. PEDF also increased the transcriptional activity of PPARgamma as evident from electromobility shift assays, and p53 as determined by the phosphorylation and acetylation of p53 and the induction of Bax. The induction of p53 by PEDF was abolished by either PPARgamma antagonist or PPARgamma siRNA. PEDF-mediated HUVEC apoptosis and cleavage of procaspases were significantly attenuated by p53 siRNA. Our observations indicate that PEDF induces HUVECs apoptosis through the sequential induction of PPARgamma and p53 overexpression," wrote T.C. Ho and colleagues, Mackay Memorial Hospital. The researchers concluded: "With the growing interest in anti-angiogenesis as a novel approach to cancer therapy, defining the mechanism of PEDF-mediated HUVEC apoptosis may facilitate the development of new therapeutics." Ho and colleagues published their study in Cardiovascular Research (PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells. Cardiovascular Research, 2007;76(2):213-23). For additional information, contact T.C. Ho, Mackay Memorial Hospital, Departments of Medical Research, Taipei, Taiwan. The publisher's contact information for the journal Cardiovascular Research is: Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands. Keywords: Taiwan, Taipei, Apoptosis Gene Therapy, Angiogenesis, Apoptosis, Biotechnology, Cancer Gene Therapy, Cardiology, Cardiovascular, Genetics, Genomics, Oncology, Treatment, Tumor Vascularization. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
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