跳转至内容
Merck
  • ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.

ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.

Proceedings of the National Academy of Sciences of the United States of America (2014-04-08)
Faraz Quazi, Robert S Molday
摘要

The visual cycle is a series of enzyme-catalyzed reactions which converts all-trans-retinal to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells. Although essential for vision, 11-cis-retinal like all-trans-retinal is highly toxic due to its highly reactive aldehyde group and has to be detoxified by either reduction to retinol or sequestration within retinal-binding proteins. Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation. How rod and cone cells prevent the accumulation of 11-cis-retinal in photoreceptor disk membranes in excess of what is required for visual pigment regeneration is not known. Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes. This transport function together with chemical isomerization to its all-trans isomer and reduction to all-trans-retinol by RDH can prevent the accumulation of excess 11-cis-retinal and its Schiff-base conjugate and the formation of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macular degeneration. This segment of the visual cycle in which excess 11-cis-retinal is converted to all-trans-retinol provides a rationale for the unusually high content of PE and its long-chain unsaturated docosahexaenoyl group in photoreceptor membranes and adds insight into the molecular mechanisms responsible for Stargardt macular degeneration.

材料
货号
品牌
产品描述

Sigma-Aldrich
视黄醇, synthetic, ≥95% (HPLC), (Powder or Powder with Lumps)
Sigma-Aldrich
视黄醇, BioXtra, ≥97.5% (HPLC), ~3100 U/mg
Sigma-Aldrich
视黄醇, ≥95.0% (HPLC), ~2700 U/mg
Supelco
维生素A标准液 溶液, 100 μg/mL ± 25% (Refer to COA) (Ethanol with 0.1% (w/v) BHT), ampule of 1 mL, reference material, Cerilliant®
Sigma-Aldrich
1,2-二油酰--甘油基-3-磷酸胆碱, lyophilized powder