tailieunhanh - Báo cáo khóa học: Induction of endothelial apoptosis by 4-hydroxyhexenal

Lipid peroxidation and its products such as 4-hydroxy-2-nonenal (HNE) and 4-hydroxyhexenal (HHE) are known to affect redox balance duringagingand various degenerative processes, includingvascular dysfunction. Deterioration of the endothelial cells that line the vascular wall is known to be an underlyingcause of vascular dysfunction. At present, little is known about themechanismbywhichHHE induces endothelial cell death (. apoptosis), although HNE-induced apoptotic cell death has been reported. . | Eur. J. Biochem. 271 1339-1347 2004 FEBS 2004 doi Induction of endothelial apoptosis by 4-hydroxyhexenal Ji Young Lee1. Jeona Hwan Je2. Dae Hvun Kim2. Sana Woon Chung2. Yani Zou2. Nam Deuk Kim1 2 IV B B FF w B B wV F F IV F FF B B vl B B V V fB B B IV FF FF FF B B V w B B B w B B B B F F FF B B fF V V FF FF B B BBB B w B B fF B FF B B B B FF w B V FF B B B FF w B w B w B B B B Mie Ae Yoo1 Hyung Suck Baik1 Byung Pal Yu3 and Hae Young Chung1 2 1Genetic Engineering Research Institute Pusan National University Busan Korea 2College of Pharmacy Aging Tissue Bank Pusan National University Busan Korea 3 Department of Physiology University of Texas Health Science Center San Antonio Texas USA Lipid peroxidation and its products such as 4-hydroxy-2-nonenal HNE and 4-hydroxyhexenal HHE are known to affect redox balance during ai ina anv riirious dí í É iatmlive processes including vasuuhir ysfi ncto n. L itteióoríitó n of the endothelial cells that line the dascular wall is known to be an underlying came of vascular dysi unciion. At pedent. little is known about the mechanism by which HHE induces endothelial cell death . apoptosis although HNE-induced apoptotic cell death has been reported. The aim of this study was to determine whether apoptosis induced by HHE in endothelial cells involves peroxynitrite ONOO- . Our results show that in endothelial cells HHE triggers apoptotic cell death by inducing apoplolic Bax coupLcI with a decrease in anti-apoptotic Bcl-2. Results show that HHE induces reactive oxygen species ROS nitric oxide and ONOO- generation leading to redox imbalance. Furthermore the antioxidant N-acetyl cysteine ROS scavenger and penicillamine an ONOO- scavenger were found to block HHE-mediated apoptosis. We used confocal laser microscopy to estimate the ability of these inhibitors to attenuate HHE-induced intracellular ONOO- levels thus confirming the xxidative maiiiaiKm fl opppCosis m nitdo-thelial cells. These findings .