Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells

被引:242
作者
Bian, Qingning [1 ,2 ]
Gao, Shasha [1 ,2 ]
Zhou, Jilin [3 ]
Qin, Jian [1 ]
Taylor, Allen [1 ]
Johnson, Elizabeth J. [1 ]
Tang, Guangwen [1 ]
Sparrow, Janet R. [3 ]
Gierhart, Dennis [4 ]
Shang, Fu [1 ,2 ]
机构
[1] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA
[2] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China
[3] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA
[4] Zeavision LLC, Chesterfield, MO 63005 USA
关键词
Lutein; Zeaxanthin; RPE; Photooxidation; Proteasome; Inflammation; COMPLEMENT FACTOR-H; NF-KAPPA-B; C-REACTIVE PROTEIN; UBIQUITIN-PROTEASOME PATHWAY; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; CONJUGATING ENZYMES; PROTEOLYTIC PATHWAY;
D O I
10.1016/j.freeradbiomed.2012.06.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Oxidative damage and inflammation are related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that insufficient dietary lutein and zeaxanthin intake or lower serum zeaxanthin levels are associated with increased risk for AMD. The objective of this work is to test the protective effects of lutein and zeaxanthin against photooxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of inflammation-related genes. To mimic lipofuscin-mediated photooxidation in vivo, we used ARPE-19 cells that accumulated A2E, a lipofuscin fluorophore and photosensitizer, as a model system to investigate the effects of lutein and, zeaxanthin supplementation. The data show that supplementation with lutein or zeaxanthin in the medium resulted in accumulation of lutein or zeaxanthin in the RPE cells. The concentrations of lutein and zeaxanthin in the cells were 2- to 14-fold of that detected in the medium, indicating that ARPE-19 cells actively take up lutein or zeaxanthin. As compared with untreated cells, exposure of A2E-containing RPE to blue light resulted in a 40-60% decrease in proteasome activity, a 50-80% decrease in expression of CFH and MCP-1, and an similar to 20-fold increase in expression of IL-8. The photooxidation-induced changes in expression of MCP-1, IL-8, and CFH were similar to those caused by chemical inhibition of the proteasome, suggesting that inactivation of the proteasome is involved in the photooxidation-induced alteration in expression of these inflammation-related genes. Incubation of the A2E-containing RPE with lutein or zeaxanthin prior to blue light exposure significantly attenuated the photooxidation-induced inactivation of the proteasome and photooxidation-induced changes in expression of MCP-1, IL-8, and CFH. Together, these data indicate that lutein or zeaxanthin modulates inflammatory responses in cultured RPE in response to photooxidation. Protecting the proteasome from oxidative inactivation appears to be one of the mechanisms by which lutein and zeaxanthin modulate the inflammatory response. Similar mechanisms may explain salutary effects of lutein and zeaxanthin in reducing the risk for AMD. (c) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:1298 / 1307
页数:10
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