| Autor: |
Jang, Geeng-Fu, Van Hooser, J. Preston, Kuksa, Vladimir, McBee, Joshua K., He, Yu-Guang, Janssen, Jacques J.M., Driessen, Carola A.G.G., Palczewski, Krzysztof |
| Zdroj: |
Journal of Biological Chemistry; August 2001, Vol. 276 Issue: 35 p32456-32465, 10p |
| Abstrakt: |
In the vertebrate retina, the final step of visual chromophore production is the oxidation of 11-cis-retinol to 11-cis-retinal. This reaction is catalyzed by 11-cis-retinol dehydrogenases (11-cis-RDHs), prior to the chromophore rejoining with the visual pigment apo-proteins. The RDH5gene encodes a dehydrogenase that is responsible for the majority of RDH activity. In humans, mutations in this gene are associated with fundus albipunctatus, a disease expressed by delayed dark adaptation of both cones and rods. In this report, an animal model for this disease,11-cis-rdh−/−mice, was used to investigate the flow of retinoids after a bleach, and microsomal membranes from the retinal pigment epithelium of these mice were employed to characterize remaining enzymatic activities oxidizing 11-cis-retinol. Lack of 11-cis-RDH leads to an accumulation ofcis-retinoids, particularly 13-cis-isomers. The analysis of 11-cis-rdh−/−mice showed that the RDH(s) responsible for the production of 11-cis-retinal displays NADP-dependent specificity toward 9-cis- and 11-cis-retinal but not 13-cis-retinal. The lack of 13-cis-RDH activity could be a reason why 13-cis-isomers accumulate in the retinal pigment epithelium of 11-cis-rdh−/−mice. Furthermore, our results provide detailed characterization of a mouse model for the human disease fundus albipunctatus and emphasize the importance of 11-cis-RDH in keeping the balance between different components of the retinoid cycle. |
| Databáze: |
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