tailieunhanh - Báo cáo khoa học: Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis

Ulcerative colitis (UC) is a gastrointestinal disorder characterized by an inflammatory process associated with mucosal damage. Many studies have shown that n-3 polyunsaturated fatty acids (PUFAs) possess anti-inflam-matory effects in inflammatory bowel disease. | ỊFEBS Journal Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis Qiurong Li1 Qiang Zhang1 Min Zhang2 Chenyang Wang1 Zhenxin Zhu1 Ning Li1 and Jieshou Li1 1 Institute of GeneralSurgery Jinling Hospital Nanjing China 2 Jiangsu Academy of Forestry Nanjing China Keywords n-3 PUFAs raft microdomain tight junction proteins ulcerative colitis Correspondence J. Li Institute of GeneralSurgery Jinling Hospital No. 305 East Zhongshan Road Nanjing 210002 China Fax 86 25 84803956 Tel 86 25 80860064 E-mail liqiurong@ Received 22 August 2007 revised 17 November 2007 accepted 27 November 2007 doi Ulcerative colitis UC is a gastrointestinal disorder characterized by an inflammatory process associated with mucosal damage. Many studies have shown that n-3 polyunsaturated fatty acids PUFAs possess anti-inflammatory effects in inflammatory bowel disease. The aim of this study was to investigate whether n-3 PUFAs could alleviate intestinal damage in experimental UC. In the present study we found that in 2 4 6-trinitrobenzene-sulfonic acid-induced colitic rats the damage to the intestinal mucosa was accompanied by a disrupted tight junction TJ structure. In accordance with these changes the distribution and expression of TJ proteins including occludin claudin-1 claudin-3 claudin-5 claudin-8 and ZO-1 in membrane microdomains was altered. The distribution of flotillin-1 a lipid raft marker protein was also changed. Moreover we found for the first time that n-3 PUFAs prevented redistribution of TJ proteins from Triton X-100-insoluble raft-like membrane microdomains to Triton X-100-soluble fractions. The expression of ZO-1 claudin-1 claudin-5 and claudin-8 was significantly elevated by n-3 PUFAs. n-3 PUFAs also attenuated the disruption of TJ structure and improved the histological score. Our results demonstrate that the expression and distribution of TJ proteins in TJ .