Premium
Human organic anion transporting polypeptide 1 A 2 ( OATP1A2 ) mediates cellular uptake of all‐ trans ‐retinol in human retinal pigmented epithelial cells
Author(s) -
Chan Ting,
Zhu Ling,
Madigan Michele C,
Wang Ke,
Shen Weiyong,
Gillies Mark C,
Zhou Fanfan
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13060
Subject(s) - microbiology and biotechnology , biology , retinal pigment epithelium , multidrug resistance associated protein 2 , organic anion transporting polypeptide , retinoid , chemistry , retinoic acid , biochemistry , retinal , transporter , atp binding cassette transporter , gene
Background and Purpose Vision depends on retinoid exchange between the retinal pigment epithelium ( RPE ) and photoreceptors. Defects in any step of the canonical visual cycle can lead to retinal degenerations. All‐ trans ‐retinol ( atROL ) plays an important role in visual signal transduction. However, how atROL enters human RPE from the apical membrane remains unclear. This study investigated the role of human organic anion transporting polypeptide 1 A 2 ( OATP1A2 ) in atROL uptake in human RPE . Experimental Approach Immunoblotting and immunostaining elucidated the expression and localization of OATP1A2 in human RPE . Transporter functional studies were conducted to assess the interaction of OATP1A2 with atROL . Key Results Our study revealed OATP1A2 is expressed in human RPE , mainly at the apical membrane. Our data also indicated atROL inhibited the uptake of the typical OATP1A2 substrate, oestrone‐3‐sulfate ( E3S ), in over‐expressing cells. Studies on the uptake of 3 H ‐ atROL in these over‐expressing cells revealed atROL is a substrate of OATP1A2 . We confirmed these findings in human primary RPE cells. The transport of E3S and atROL was significantly reduced in human primary RPE cells with OATP1A2 siRNA silencing. Conclusion and Implications Our data provides the first evidence of OATP1A2 expression in human RPE and more importantly, its novel role in the cellular uptake of atROL , which might be essential to the proper functioning of the canonical visual cycle. Our findings contribute to the understanding of the molecular mechanisms involved in retinoid transport between the RPE and photoreceptors and provide novel insights into potential pharmaceutical interventions for visual cycle disruption associated with retinal degenerations.