tailieunhanh - Báo cáo khoa học: Upregulation of endothelial adhesion molecules by lysophosphatidylcholine

Lysophosphatidylcholine induces expression of adhesion molecules; how-ever, the underlying molecular mechanisms of this are not well elucidated. In this study, the intracellular signaling by which lysophosphatidylcholine upregulates vascular cell adhesion molecule-1 and P-selectin was delineated using YPEN-1 and HEK293T cells. | ỊFEBS Journal Upregulation of endothelial adhesion molecules by lysophosphatidylcholine Involvement of G protein-coupled receptor GPR4 Yani Zou1 Chul H. Kim1 Jae H. Chung1 Ji Y. Kim1 Sang W. Chung1 Mi K. Kim2 Dong S. Im1 Jaewon Lee1 Byung P. Yu2 3 and Hae Y. Chung1 2 1 College of Pharmacy Pusan National university Busan Korea 2 Longevity Life Science Technology Institute Pusan NationalUniversity Busan Korea 3 Department of Physiology University of Texas Health Science Center San Antonio TX USA Keywords adhesion molecules cAMP response element-binding protein G protein-coupled receptor 4 lysophosphatidylcholine nuclear factor kappaB Correspondence H. Y. Chung Longevity Life Science Technology Institute College of Pharmacy Pusan NationalUniversity 30 Jangjun-dong Gumjung-gu Busan 609-735 Korea Fax 82 51 518 2821 Tel 82 51 510 2814 E-mail hyjung@ Received 2 December 2006 revised 11 February 2007 accepted 15 March 2007 doi Lysophosphatidylcholine induces expression of adhesion molecules however the underlying molecular mechanisms of this are not well elucidated. In this study the intracellular signaling by which lysophosphatidylcholine upregulates vascular cell adhesion molecule-1 and P-selectin was delineated using YPEN-1 and HEK293T cells. The results showed that lysophos-phatidylcholine dose-dependently induced expression of vascular cell adhesion molecule-1 and P-selectin accompanied by the activation of transcription factor nuclear factor kB. However the nuclear factor kB inhibitor caffeic acid phenethyl ester CAPE and the antioxidant N-acetylcysteine only partially blocked lysophosphatidylcholine-induced adhesion molecules. Subsequently we found that the lysophosphatidylcholine receptor G protein-coupled receptor 4 GPK4 was expressed in YPEN-1 cells and triggered the cAMP protein kinase A cAMP response element-binding protein pathway resulting in upregulation of adhesion molecules. Further evidence showed that .