Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in retina in hemochromatosis and by the endogenous siderophore 2,5-dihydroxybenzoic acid.
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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DOI：
10.1016/j.bbadis.2014.01.010
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发表时间：
2014-04
影响因子：
6.2
通讯作者：
Ganapathy, Vadivel
中科院分区：
文献类型：
--
作者：
Ananth, Sudha;Gnana-Prakasam, Jaya P.;Bhutia, Yangzom D.;Veeranan-Karmegam, Rajalakshmi;Martin, Pamela M.;Smith, Sylvia B.;Ganapathy, Vadivel
关键词：
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 (Hfe−/−) 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 Hfe−/− 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 Hfe−/− 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 Hfe−/− 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.
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影响因子：
4.4
作者：
Hadziahmetovic, Majda;Song, Ying;Dunaief, Joshua L.
通讯作者：
Dunaief, Joshua L.
DOI：
10.1042/bj20090424
发表时间：
2009-11-11
期刊：
The Biochemical journal
影响因子：
--
作者：
Gnana-Prakasam JP;Thangaraju M;Liu K;Ha Y;Martin PM;Smith SB;Ganapathy V
通讯作者：
Ganapathy V
影响因子：
3.6
作者：
Dun, Y;Mysona, B;Smith, SB
通讯作者：
Smith, SB
DOI：
10.1136/bjo.2008.144006
发表时间：
2009-08
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Duncan KG;Hosseini K;Bailey KR;Yang H;Lowe RJ;Matthes MT;Kane JP;LaVail MM;Schwartz DM;Duncan JL
通讯作者：
Duncan JL
DOI：
10.1042/bj20111148
发表时间：
2012-01-15
期刊：
The Biochemical journal
影响因子：
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作者：
Gnana-Prakasam JP;Tawfik A;Romej M;Ananth S;Martin PM;Smith SB;Ganapathy V
通讯作者：
Ganapathy V