Molecular Characterization of a Novel Short-chain Dehydrogenase/Reductase That Reduces All-trans-retinal

Haeseleer, Françoise; Huang, Jing; Lebioda, Lukasz; Saari, John C.; Palczewski, Krzysztof

doi:10.1074/jbc.273.34.21790

Cited by 157 publications

(185 citation statements)

References 42 publications

(49 reference statements)

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“…Although the reverse reaction is also catalyzed but with at least 10-fold lower efficiency. Our findings are in agreement with previously published reports whereby RDH11, RDH12, RDH14 and RetSDR1 are shown to specifically prefer the phosphorylated coenzyme, and catalyze the reduction over the oxidation reaction (Haeseleer, Huang, Lebioda, Saari and Palczewski, 1998;Rattner, Smallwood and Nathans, 2000). RDH13 has been shown before to completely lack catalytic activity towards retinoids (Haeseleer, Jang, Imanishi, Driessen, Matsumura, Nelson and Palczewski, 2002) therefore it is not expected to contribute to the total RDH activity measured here.…”

Section: Dehydrogenases In the 661w Cells Act As Reductases Rather Thsupporting

confidence: 94%

“…Dehydrogenases RDH13 and 14 are the highest expressed transcripts and are comparably expressed in both models. RetSDR1, a dehydrogenase that has cone specific location (Haeseleer, Huang, Lebioda, Saari and Palczewski, 1998), is expressed to greater levels in 661W cells and Nrl −/− retina compared to WT retina ( Figure 2A, B & C). Overall, it is clear that 661W cell resembles the 'all cone' Nrl −/− retina more than the rod dominated C57BL/6J retina.…”

Section: Conversion Of Atr To Atol and Retinyl Ester In 661w Cellsmentioning

confidence: 99%

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Retinoid processing in cone and Müller cell lines

Kanan

Kasus‐Jacobi

Moiseyev

et al. 2008

Experimental Eye Research

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To determine whether cones and Müller cells in the rod dominated retina, cooperate to regenerate the 11-cis retinal chromophore via the retinoid cycle, two cell lines from the rod dominated retinas of Murine were used for this study, 661W a mouse cell line derived from cones and rMC-1, a rat Müller cell line. Retinoid cycle enzymes were analyzed by RT-PCR and their catalytic activity were detected by incubation with retinoids and analyzed by HPLC. We found that, 661W cells are capable of reducing all-trans retinal to all-trans retinol due to the presence of multiple dehydrogenases and generate minor amounts of retinyl-ester. The rMC-1 cells take up all-trans retinol and oxidizes it to all-trans retinal or esterify it to retinyl-ester, but are incapable of isomerizing all-trans retinoids to 11-cis retinoids. This could be a reflection of lack of necessary activities in Müller cells in vivo which suggests that Müller cells do not contribute to retinoid cycling by regenerating 11-cis retinoids. Alternatively, this could be due to the potential that rMC-1, as a transformed cell line, has stopped expressing the proteins needed for the regeneration of 11-cis retinoids.

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Section: Dehydrogenases In the 661w Cells Act As Reductases Rather Thsupporting

confidence: 94%

Section: Conversion Of Atr To Atol and Retinyl Ester In 661w Cellsmentioning

confidence: 99%

Retinoid processing in cone and Müller cell lines

Kanan

Kasus‐Jacobi

Moiseyev

et al. 2008

Experimental Eye Research

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“…Efforts to identify the RDH enzymes essential for visual cycle function have been confounded by the fact that photoreceptor cells express a number of isoforms which exhibit the necessary specificity in vitro (10,43,57) (Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

Chrispell¹,

Feathers

Kane

et al. 2009

Journal of Biological Chemistry

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RDH12 mutations are responsible for early-onset autosomal recessive retinal dystrophy, which results in profound retinal pathology and severe visual handicap in patients. To investigate the function of RDH12 within the network of retinoid dehydrogenases/reductases (RDHs) present in retina, we studied the retinal phenotype of Rdh12-deficient mice. In vivo rates of alltrans-retinal reduction and 11-cis-retinal formation during recovery from bleaching were similar in Rdh12-deficient and wild-type mice matched for an Rpe65 polymorphism that impacts visual cycle efficiency. However, retinal homogenates from Rdh12-deficient mice exhibited markedly decreased capacity to reduce exogenous retinaldehydes in vitro. Furthermore, in vivo levels of the bisretinoid compound diretinoid-pyridinium-ethanolamine (A2E) were increased in Rdh12-deficient mice of various genetic backgrounds. Conversely, in vivo levels of retinoic acid and total retinol were significantly decreased. Rdh12 transcript levels in wild-type mice homozygous for the Rpe65-Leu 450 polymorphism were greater than in Rpe65-Met 450 mice and increased during postnatal development in wild-type mice and Nrl-deficient mice having an all-cone retina. Rdh12-deficient mice did not exhibit increased retinal degeneration relative to wild-type mice at advanced ages, when bred on the lightsensitive BALB/c background, or when heterozygous for a null allele of superoxide dismutase 2 (Sod2 ؉/؊ ). Our findings suggest that a critical function of RDH12 is the reduction of all-trans-retinal that exceeds the reductive capacity of the photoreceptor outer segments.RDH12 is a major disease gene for Leber congenital amaurosis, with RDH12 mutations responsible for approximately 2% of cases of childhood-onset severe autosomal recessive retinal dystrophy (1-4). Affected individuals experience poor vision in early life, which progressively declines with age as a result of both rod and cone degeneration (5). Analyses of retinal organization and visual function in patients with mutations in RDH12 or RPE65, another Leber congenital amaurosis gene involved in retinoid metabolism, show distinctly different pathologies associated with defects in each gene that will be important to consider when developing targeted forms of therapy (6).RDH12 encodes a member of the family of short chain dehydrogenases/reductases that catalyze oxidation and reduction reactions involved in various aspects of metabolism (reviewed in Refs. 7 and 8). In the photoreceptor cells and retinal pigment epithelium (RPE), 3 the interconversion of oxidized and reduced retinoids by RDH enzymes is an important feature of the visual cycle, the process responsible for the conversion of vitamin A (all-trans-retinol) to 11-cis-retinal, the chromophore of the visual pigments (reviewed in Ref. 9). On the basis of in vitro assays showing reactivity toward retinaldehyde substrates and expression in photoreceptor cells, RDH12 was initially proposed to function in the reduction of all-trans-retinal released by bleached visual pigments (10...

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“…Upon arrival in RPE cells, all-trans ROL is esterified into retinylesters (REs) by the lecithin:retinol acyltransferase LRAT (Mondal et al, 2000;Ruiz et al, 1999;Saari and Bredberg, 1989;Saari et al, 1993), and then isomerized to 11-cis ROL by the isomerase RPE65 (or Isomerase I) (Gollapalli and Rando, 2003;Jin et al, 2005;Moiseyev et al, 2005;Redmond et al, 2005). Finally, 11-cis ROL is oxidized to 11-cis RAL by a retinol dehydrogenase (Cideciyan et al, 2000;Driessen et al, 1997;Gamble et al, 2000;Haeseleer et al, 1998;Lion et al, 1975;Simon et al, 1999;Suzuki et al, 1993). The recycled 11-cis RAL is transported back to photoreceptor outer segments where it re-assembles with the opsin to form functional visual pigment (Bok, 1985;Pepperberg and Clack, 1984) ( Figure 1).…”

Section: Canonical Retinoid Recycling In Vertebrate Eyesmentioning

confidence: 99%

Parallel visual cycles in the zebrafish retina

Fleisch

2010

Progress in Retinal and Eye Research

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Vertebrate vision necessitates continuous recycling of the chromophore 11-cis retinal (RAL). The classical (or canonical) visual cycle employs a number of enzymes located in the photoreceptor outer segment and RPE (retinal pigment epithelium) of the retina to regenerate 11-cis RAL from all-trans RAL. Cone-dominant species are believed to utilize a second, intra-retinal, pathway for 11-cis RAL generation, involving retinal Müller glia cells. This review summarizes the efforts made in zebrafish to gain a better understanding of the role of these two visual cycles for rod and cone photoreceptor chromophore recycling.

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Molecular Characterization of a Novel Short-chain Dehydrogenase/Reductase That Reduces All-trans-retinal

Cited by 157 publications

References 42 publications

Retinoid processing in cone and Müller cell lines

Retinoid processing in cone and Müller cell lines

Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

Parallel visual cycles in the zebrafish retina

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