کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8260376 | 1534661 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in retina in hemochromatosis and by the endogenous siderophore 2,5-dihydroxybenzoic acid
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کلمات کلیدی
PMCPGC5-AzacytidineABCG15-Aza-C2,5-DHBARPEABCA1TFRAMD2,5-dihydroxybenzoic acid - 2،5-دی هیدروکسی بنزوئیک اسیدATP-binding cassette transporter A1 - ATP اتصال گیرنده کاست A1ATP-binding cassette transporter G1 - G1 حمل کننده کاسه اتصال ATPCholesterol transport - انتقال کلسترولretinal pigment epithelium - اپیتلیوم رنگدانه شبکیهRetinal pigment epithelial cells - سلول های اپیتلیال رنگدانه شبکیهage-related macular degeneration - سن تخریب ماکولا مربوط به سن استHAMP - هامپHemochromatosis - هموکروماتوزtransferrin receptor - گیرنده انتقالین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Hypercholesterolemia and polymorphisms in the cholesterol exporter ABCA1 are linked to age-related macular degeneration (AMD). Excessive iron in retina also has a link to AMD pathogenesis. Whether these findings mean a biological/molecular connection between iron and cholesterol is not known. Here we examined the relationship between retinal iron and cholesterol using a mouse model (Hfeâ/â) of hemochromatosis, a genetic disorder of iron overload. We compared the expression of the cholesterol efflux transporters ABCA1 and ABCG1 and cholesterol content in wild type and Hfeâ/â mouse retinas. We also investigated the expression of Bdh2, the rate-limiting enzyme in the synthesis of the endogenous siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA) in wild type and Hfeâ/â mouse retinas, and the influence of this siderophore on ABCA1/ABCG1 expression in retinal pigment epithelium. We found that ABCA1 and ABCG1 were expressed in all retinal cell types, and that their expression was decreased in Hfeâ/â retina. This was accompanied with an increase in retinal cholesterol content. Bdh2 was also expressed in all retinal cell types, and its expression was decreased in hemochromatosis. In ARPE-19 cells, 2,5-DHBA increased ABCA1/ABCG1 expression and decreased cholesterol content. This was not due to depletion of free iron because 2,5-DHBA (a siderophore) and deferiprone (an iron chelator) had opposite effects on transferrin receptor expression and ferritin levels. We conclude that iron is a regulator of cholesterol homeostasis in retina and that removal of cholesterol from retinal cells is impaired in hemochromatosis. Since excessive cholesterol is pro-inflammatory, hemochromatosis might promote retinal inflammation via cholesterol in AMD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1842, Issue 4, April 2014, Pages 603-612
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1842, Issue 4, April 2014, Pages 603-612
نویسندگان
Sudha Ananth, Jaya P. Gnana-Prakasam, Yangzom D. Bhutia, Rajalakshmi Veeranan-Karmegam, Pamela M. Martin, Sylvia B. Smith, Vadivel Ganapathy,