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ABSTRACT: Oxidative stress induces retinal damage and contributes to vision loss in progressive retinopathies. Carcinine (β-alanyl-histamine) is a natural imidazole-containing peptide derivative with antioxidant activity. It is predicted to scavenge 4-hydroxynonenal (4-HNE), a toxic product of lipid oxidation. The aim of this study was to confirm the 4-HNE scavenging effect and evaluate the neuroprotective effect of carcinine in mouse retina subjected to oxidative stress.
HPLC coupled with mass spectrometry was used to analyze carcinine and 4-HNE-carcinine adduct. Protection of retinal proteins from modification by 4-HNE was tested by incubating carcinine with retinal protein extract and 4-HNE. Modified retinal proteins were quantified by dot-blot analysis. Mice were treated with carcinine (intravitreal injection and gavage) and exposed to bright light to induce oxidative damage in the retina. Photoreceptor degeneration was measured by histology and electroretinography. Retinal levels of retinol dehydrogenase 12 (RDH12) were measured by immunoblot analysis, after exposure to bright light and in retinal explants after exposure to 4-HNE.
The ability of carcinine to form an adduct with 4-HNE, as well as to prevent and even reverse the adduction of retinal proteins by the toxic aldehyde was demonstrated in vitro. Carcinine, administered by intravitreal injection or gavage, strongly protected mouse retina against light-induced photoreceptor degeneration and had a protective effect on RHD12, a protein found specifically in photoreceptor cells.
This study suggests that carcinine can be administered noninvasively to efficiently protect photoreceptor cells from oxidative damage. Carcinine could be administered daily to prevent vision loss in progressive retinopathies.
Investigative ophthalmology & visual science 05/2012; 53(7):3572-83. · 3.43 Impact Factor
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03/2012; , ISBN: 978-953-51-0248-9
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ABSTRACT: The latest estimates of the World Health Organization indicate that there are 161 million visually impaired individuals worldwide, 37 million of whom are blind, with a yearly increase of 1-2 million. The scientists developed and patented the lubricant eye drops formulated as 1%N-acetylcarnosine prodrug of l-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in an ocular drug delivery system. Carcinine is suitable for the systemic administration (per oral) for ophthalmic therapeutic indications. The HPLC analysis was developed to search the pathways of ocular metabolic activities of 1%N-acetylcarnosine and the bioactivation of this drug molecule promoting transcorneal uptake of l-carnosine in the aqueous humor. A meta-analysis of phase 2 randomized double-blind placebo-controlled clinical trial data was conducted. The intraocular absorbed l-carnosine demonstrated a number of pharmacological mechanisms of prevention and reversal of cataracts. Results of systemic absorption of l-carnosine provide tuberomammillary activation that regulates neuronal functions such as hypothalamic control promoting sensory input in the primary vision perceptual pathway. The parabulbar, subconjunctival, and intravitreal injection of carcinine with most of the vehicle removed is not toxic to intraocular structures, reduces postoperative intraocular inflammation, is a potentially useful tool in the treatment of proliferative vitreoretinopathy as well as considered as the antiapoptotic drug for the protection of photoreceptor cells from oxidative light-induced stress. The discovery of naturally occurring carnosine derivatives introduces N-acetylcarnosine and carcinine as effective medical treatment for sight-threatening eye disorders.
Fundamental and Clinical Pharmacology 07/2011; 26(5):644-78. · 1.80 Impact Factor
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Md Nawajes A Mandal,
Gennadiy P Moiseyev,
Michael H Elliott, Anne Kasus-Jacobi,
Xiaoman Li,
Hui Chen,
Lixin Zheng,
Olga Nikolaeva,
Robert A Floyd,
Jian-Xing Ma,
Robert E Anderson
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ABSTRACT: α-Phenyl-N-tert-butylnitrone (PBN), a free radical spin trap, has been shown previously to protect retinas against light-induced neurodegeneration, but the mechanism of protection is not known. Here we report that PBN-mediated retinal protection probably occurs by slowing down the rate of rhodopsin regeneration by inhibiting RPE65 activity. PBN (50 mg/kg) protected albino Sprague-Dawley rat retinas when injected 0.5-12 h before exposure to damaging light at 2,700 lux intensity for 6 h but had no effect when administered after the exposure. PBN injection significantly inhibited in vivo recovery of rod photoresponses and the rate of recovery of functional rhodopsin photopigment. Assays for visual cycle enzyme activities indicated that PBN inhibited one of the key enzymes of the visual cycle, RPE65, with an IC(50) = 0.1 mm. The inhibition type for RPE65 was found to be uncompetitive with K(i) = 53 μm. PBN had no effect on the activity of other visual cycle enzymes, lecithin retinol acyltransferase and retinol dehydrogenases. Interestingly, a more soluble form of PBN, N-tert-butyl-α-(2-sulfophenyl) nitrone, which has similar free radical trapping activity, did not protect the retina or inhibit RPE65 activity, providing some insight into the mechanism of PBN specificity and action. Slowing down the visual cycle is considered a treatment strategy for retinal diseases, such as Stargardt disease and dry age-related macular degeneration, in which toxic byproducts of the visual cycle accumulate in retinal cells. Thus, PBN inhibition of RPE65 catalytic action may provide therapeutic benefit for such retinal diseases.
Journal of Biological Chemistry 07/2011; 286(37):32491-501. · 4.77 Impact Factor
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ABSTRACT: Evaluation of: Attanasio F, Cataldo S, Fisichella S et al. Protective effects of L- and D-carnosine on α-crystallin amyloid fibril formation: implications for cataract disease. Biochemistry 48(27), 6522-6531 (2009).We shall evaluate a paper examining protective and therapeutic significance of carnosine derivatives that have been formerly proposed as potent agents for ophthalmic therapies of senile cataracts and diabetic ocular complications. The authors report the inhibitory effect induced by the racemized carnosine peptides (L- and D-enantiomeric forms) on the modulation of fibrillation of cataract disease-related α-crystallin. The latter molecular chaperone protects against the unfolding and aggregation of lens crystallins and oxidative stress toxicity to the lens proteins. The authors have found a disassembling effect of racemized carnosine forms on α-crystallin amyloid fibrils, and the almost complete restoration of the chaperone activity lost has been revealed after denaturant and/or heat stress. This article supports the ability of carnosine dipeptide to restore most of the lens transparency in cataractous lenses (short-term organ-cultured rat lenses). The entire body of supporting published research on N-acetylcarnosine and its bioactivated principle carnosine reveals its promise as a water-soluble universal antioxidant that works at several levels to defend against the oxidative stresses to the lens and glycosylation problems, and to protect the lens proteins and the membrane lipids from oxidative damages, thus preventing and reversing age-related cataract in human eyes.
Expert Review of Ophthalmology 11/2009; 4(6):581-586.
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ABSTRACT: Mutations of the photoreceptor retinol dehydrogenase 12 (RDH12) gene cause the early onset retinal dystrophy Leber congenital amaurosis (LCA) by mechanisms not completely resolved. Determining the physiological role of RDH12 in photoreceptors is the focus of this study. Previous studies showed that RDH12, and the closely related retinol dehydrogenase RDH11, can enzymatically reduce toxic lipid peroxidation products such as 4-hydroxynonenal (4-HNE), in vitro. To explore the significance of this activity, we investigated the ability of RDH11 and RDH12 to protect stably transfected HEK-293 cells against the toxicity of 4-HNE. Both enzymes protected against 4-HNE modification of proteins and 4-HNE-induced apoptosis in HEK-293 cells. In the retina, exposure to bright light induced lipid peroxidation, 4-HNE production, and 4-HNE modification of proteins in photoreceptor inner segments, where RDH11 and RDH12 are located. In mouse retina, RDH12-but not RDH11-protected against adduct formation, suggesting that 4-HNE is a physiological substrate of RDH12. RDH12-but not RDH11-also protected against light-induced apoptosis of photoreceptors. We conclude that in mouse retina RDH12 reduces 4-HNE to a nontoxic alcohol, protecting cellular macromolecules against oxidative modification and protecting photoreceptors from light-induced apoptosis. This activity is of particular significance to the understanding of the molecular mechanisms of RDH12-induced LCA.
Free radical biology & medicine 09/2009; 48(1):16-25. · 5.42 Impact Factor
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ABSTRACT: The antioxidant activity of L-carnosine (beta-alanyl-L-histidine, bioactivated in ocular tissues) versus N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine, ocular-targeted small dipeptide molecules) was studied in aqueous solution and in a lipid environment, employing liposomes as a model of lipid membranes. Reactive oxygen species (ROS) were generated by an iron/ascorbate promoter system for induction of lipid peroxidation (LPO). L-carnosine, which is stabilized from enzymatic hydrolysis, operates as a universal aldehyde and ROS scavenger in both aqueous and lipid environments and is effective at preventing ROS-induced damage to biomolecules. Second-generation carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and tested versus L-carnosine for their ability to reverse the glycation process, also known as the Maillard reaction, and reverse the stable intermolecular cross-links, monitored in the glucose-ethylamine Schiff base model, ultimately resulting in the formation of the advanced glycation end products (AGEs) from nonenzymatic glycation, accumulating in numerous body tissues and fluids. The obtained data demonstrate the transglycation properties of the ophthalmically stabilized L-carnosine and L-carnosine histidyl-hydrazide derivatives tested and can be used to decrease or predict the occurrence of long-term complications of AGE formation and improve therapeutically the quality of vision and length of life for diabetes mellitus patients and survivors with early aging. Scientists at Innovative Vision Products, Inc. (IVP), developed lubricant eyedrops designed as a sustained-release 1% N-acetylcarnosine prodrug of L-carnosine. The eyedrops contain a mucoadhesive cellulose-based compound combined with corneal absorption promoters and glycerine in a drug-delivery system. Anti-aging therapeutics with the ophthalmic drug eyedrop formula including N-acetylcarnosine showed efficacy in the nonsurgical treatment of age-related cataracts for enrolled participants in the prospective, randomized, double-masked, placebo-controlled crossover clinical trial after controlling for age, gender, and daily activities. In a cohort in excess of 50,500 various patients seeking cutting-edge medical care, the N-acetylcarnosine topical eyedrops target therapy was demonstrated to have significant efficacy, safety, and good tolerability for the prevention and treatment of visual impairment in this older population with relatively stable patterns of causes for blindness and visual impairment. Overall, accumulated study data demonstrate that the IVP-designed new vision-saving drugs, including N-acetylcarnosine eyedrops, promote health vision and prevent vision disability from senile cataracts, primary open-angle glaucoma, age-related macular degeneration, diabetic retinopathy, and aging. N-acetylcarnosine eyedrop therapy is the crown jewel of the anti-aging medical movement and revolutionizes early detection, treatment, and rejuvenation of aging-related eye-disabling disorders. N-acetylcarnosine, as an innovative medical science tool and component of the home medicine and alternative medicine approaches, has the potential to alleviate visual impairment and its associated social, economic, and political woes for an aging population.
American journal of therapeutics 06/2009; 16(6):517-33.
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ABSTRACT: The exact biological functions of the aminoacyl-histidine dipeptides in ophthalmology are still unknown but they are the subject of intensive research activities at Innovative Vision Products, Inc. (IVP). Numerous studies have demonstrated, both at the tissue and organelle levels, that naturally occuring imidazole containing peptidomimetics possess strong and specific antioxidant properties, by preventing and reducing the accumulation of oxidised products derived from the lipid peroxidation (LPO) of biological membranes. Carnosine has been shown to act as a competitive inhibitor of the non-enzymatic glycosylation of proteins.Thus, carnosine may prevent and reverse (de-link) the formation of the advanced glycation end-products (AGEs), whose accumulation in the ocular tissues has been proposed to play a direct role in the etiology and pathogenesis of cataract and diabetic ocular complications (DOC). Besides, histidine-containing dipeptides are believed to act as cytosolic buffering agents.
To compare the efficacy of L-carnosine and derivatives in inhibiting/reversing oxidative stress-induced reactions relevant for cataract pathogenesis. To assess the transglycation activity of carnosine versus representatives of a new group of synthetic carnosine histidyl-hydrazide analogs. To test the clinical efficacy of N-acetylcarnosine prodrug eye drops, developed by IVP's scientists, in decreasing the symptoms of age-related cataract.
Antioxidant activity of L-carnosine and N-acetylcarnosine was studied in liposomes, a model of lipid membranes. Iron/ascorbate was used for induction of LPO and peroxidation products were measured. Second-generation carnosine analogs were synthesized and tested vs. L-carnosine for their ability to reverse the glycation process, ultimately resulting in the formation of the AGEs. Visual acuity and glare sensitivity was measured before and after 9-month of topical administration of N-acetylcarnosine eye drops in a randomized placebo-controlled cohort of patients presenting age-related uncomplicated cataract and non-cataract subjects of the same age range.
L-carnosine operates as aldehyde and reactive oxygen species (ROS) scavenger in aqueous and lipid environments, preventing ROS-induced damage to biomolecules. L-carnosine and histidyl-hydrazide analogs present transglycation properties which could be used to decrease the occurrence of long term complications of AGE formation in DOC and age-related cataracts. In the patented ophthalmic formulations, the designed leucyl-histidylhydrazide (not hydrolizable by carnosinase substrate) is endowed with a highly evolved structure optimized for the bioactivation of a N-acetylcarnosine dipeptide prodrug, targeting therapeutics of the main DOC: cataract, diabetic retinopathy, central retinal vein occlusion, central retinal artery occlusion and neovascular glaucoma. Besides, the data support the clinical application of N-acetylcarnosine lubricant eye drops to compensate corneal acidosis. Nine-month treatment with N-acetylcarnosine resulted in improved visual acuity in subjects with cataract. Glare sensitivity was improved in subjects with cataract and in non-cataract older subjects. The results from the matched studies indicate that the N-acetylcarnosine-laden therapeutic contact lenses increasing the intraocular and systemic absorption of the active dipeptide carnosine ingredient, are an effective and well-tolerated bandage lens for anterior segment disease and for post-operative management of LASEK patients.This allows practitioners to prescribe extended wear of therapeutic contact lenses loaded with N-acetylcarnosine during medical treatment of cataracts, ocular complications of diabetes, primary open-angle glaucoma and potentially creates a healthier eye and body environment during healing. A number of clinically developed with alliance groups famous International brands of patented by IVP N-acetylcarnosine lubricant eye drops (Can-C, IVP C and D-Smile) are described with a quick reference guide for completing a vendor official registration in EC countries, U.A.E., Indonesia, Japan for human and veterinary use. In a separate development series of data Carcinine (beta-alanylhistamine) significantly protected photoreceptors against light-induced apoptosis, suggesting that this compound is sufficiently resistant to degradation with enzymatic hydrolysis and can be used in vivo representing new strategies in the anti-apoptotic ophthalmic therapy.
Cataract is a major disease both in terms of number of people involved and economic impact. The research into causative factors and mechanisms to prevent the development of cataract is essential, particularly in developing countries where cataract surgery is often inaccessible. The results of this study provide a substantial basis for further evaluation of N-acetylcarnosine eye drops patented by IVP in the treatment and prevention of visual impairment in the temporal cross-sections of an older population several years apart. In the number of promotion studies this ophthalmic drug showed experimental and clinical potential for the non-surgical treatment of age-related cataracts. Comprehensive studies that investigate clinical, economic, and humanistic outcomes for the patient and society are conducted and will be described with different types of identified pharmacoeconomic evaluations to adequately assess the comparative value of current N-acetylcarnosine eye drops therapeutics for medical care and its place in future ophthalmic practices. Patients and the public expect that safe and cost-effective cataract medical care with N-acetylcarnosine therapeutic platform should be commissioned for them.
Current Clinical Pharmacology 02/2009; 4(1):4-37.
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ABSTRACT: Age-related macular degeneration (AMD) is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. In search of effective therapeutic agents, we tested curcumin, a naturally occurring compound with known anti-inflammatory and antioxidative properties, in a rat model of light-induced retinal degeneration (LIRD) and in retina-derived cell lines. We hypothesized that any compound effective against LIRD, which involves significant oxidative stress and inflammation, would be a candidate for further characterization for its potential application in AMD. We observed significant retinal neuroprotection in rats fed diets supplemented with curcumin (0.2% in diet) for 2 weeks. The mechanism of retinal protection from LIRD by curcumin involves inhibition of NF-kappaB activation and down-regulation of cellular inflammatory genes. When tested on retina-derived cell lines (661W and ARPE-19), pretreatment of curcumin protected these cells from H(2)O(2)-induced cell death by up-regulating cellular protective enzymes, such as HO-1, thioredoxin. Since, curcumin with its pleiotropic activities can modulate the expression and activation of many cellular regulatory proteins such as NF-kappaB, AKT, NRF2, and growth factors, which in turn inhibit cellular inflammatory responses and protect cells; we speculate that curcumin would be an effective nutraceutical compound for preventive and augmentative therapy of AMD.
Free radical biology & medicine 01/2009; 46(5):672-9. · 5.42 Impact Factor
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ABSTRACT: AIMS: In human diabetes, the deleterious effects of chronic hyperglycemia are the result of excessive nonenzymatic modification of proteins and phospholipids by glucose and its by-products leading to the formation of irreversible oxidized, aromatic, and fluorescent ligands known as advanced glycation end products. This glycation process has been associated with deleterious health effects. The present invention provides the potent inhibitors of protein glycation and AGEs formation, which are particularly advantageous for eyedrop delivery in the prevention and treatment of diabetes- and age-related pathologies. MAIN METHODS AND KEY FINDINGS: We proposed a deglycation system involving removal, by transglycation of sugar or aldehyde moieties from the Schiff bases by ophthalmic aldehyde scavenger L-carnosine derived from its ocular bioactivating sustained release prodrug 1% N-acetylcarnosine (NAC) lubricant eyedrops containing a mucoadhesive cellulose compound combined with corneal absorption promoters in drug delivery system. Carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and patented in ophthalmic formulations with NAC bioactivating prodrug to moderate the enzymatic hydrolysis of a dipeptide by carnosinase (inhibited by a nonhydrolyzable substrate analog so that this keeps steadier levels of the drug active principle in the aqueous humor). Leucyl-histidylhydrazide peptidomimetic demonstrated the transglycation activity more pronounced than L-carnosine accounting for the ability of either molecule to reverse pre-existing, glycation-induced, cross-linking, and checking the nonenzymatic glycation cascade in the ophthalmic pathologies. The ophthalmic drug N-acetylcarnosine eye drop formulation with sustained time- release and increased absorption of L-carnosine in the aqueous humor (a prolonged effective dose) showed follow-up treatment efficacy for age-related cataracts for enrolled patients into the randomized double blind placebo controlled crossover clinical trial, and in over 50250 various cohort patients, was demonstrated to have an efficacy, safety and good tolerability for prevention and treatment of visual impairment in the older population data base. SIGNIFICANCE: The bioactivating antioxidant NAC and histidyl-hydrazide are potent agents with the pleiotropic effects for ophthalmic therapy of senile cataracts and diabetic ocular complications.
Journal of Drug Targeting 12/2008; 17(1):36-63. · 2.70 Impact Factor
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ABSTRACT: RDH11 and RDH12 are closely related retinol dehydrogenases expressed in the retina. RDH12 has been linked to the early-onset retinal dystrophy Leber congenital amaurosis, whereas RDH11 has not been associated with human disease. To understand their physiological roles, the authors investigated their expression during development and their regulation by light-induced oxidative stress in mouse retina.
Quantitative RT-PCR and immunoblot analysis were used for quantification of RDH11 and RDH12 during development and oxidative stress. Expression during development was measured between embryonic day (E) 12 and postnatal day (P) 210 (7 months) in C57BL/6 mouse eyes. Expression during light-induced oxidative stress was measured between 2 and 24 hours of exposure to light in BALB/c mouse retina.
The RDH11 level was low and remarkably constant during development and oxidative stress. RDH12 expression started at P7 and increased until P30 to approximately sevenfold higher than RDH11. Oxidative stress induced by exposure to constant bright light led to a rapid and significant decrease of RDH12 protein.
The low and constant expression of RDH11 suggested a housekeeping function for this enzyme. The onset of RDH12 expression during the maturation of photoreceptor cells suggested a function related to the visual process. The light-induced rapid decrease of RDH12 protein, preceding the decrease of the mRNA, suggested a specific degradation of the protein rather than a regulation of gene expression.
Investigative Ophthalmology & Visual Science 04/2008; 49(3):1071-8. · 3.60 Impact Factor
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ABSTRACT: 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 was 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 to generate minor amounts of retinyl-ester. The rMC-1 cells take up all-trans retinol and oxidize 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.
Experimental Eye Research 03/2008; 86(2):344-54. · 3.26 Impact Factor
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Advances in experimental medicine and biology 02/2008; 613:61-7. · 1.09 Impact Factor
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Advances in experimental medicine and biology 02/2006; 572:505-11. · 1.09 Impact Factor
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ABSTRACT: We previously cloned mouse RDH11 (mRDH11) as a gene regulated by the transcription factor sterol regulatory element-binding proteins and showed that it is a retinol dehydrogenase expressed in non-ocular tissues such as the liver and testis and in the retina (Kasus-Jacobi, A., Ou, J., Bashmakov, Y. K., Shelton, J. M., Richardson, J. A., Goldstein, J. L., and Brown, M. S. (2003) J. Biol. Chem. 278, 32380-32389). It was proposed to function in the recycling of the visual chromophore 11-cis-retinal after photoisomerization by a bleaching light, a pathway referred to as the visual cycle. In this work, we describe our studies on the ocular function of mRDH11. We created a knockout mouse by replacing the mrdh11 coding sequence with the lacZ reporter gene for expression profiling. 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining demonstrated active transcription of this gene in photoreceptor cells. We show by immunoblot analysis that mRDH11 is associated with retinal membranes purified from a non-outer segment fraction of the retina. No obvious retinal defect was found during development and aging of RDH11-deficient mice. The functional consequences of mRDH11 disruption were investigated by electroretinography. Dark adaptation was delayed by a factor of 2.5-3 compared with wild-type mice. However, the kinetics of 11-cis-retinal recycling during dark adaptation was not affected, suggesting that mRDH11 is not involved in the visual cycle. We propose that mRDH11 disruption affects retinoid metabolism in photoreceptor inner segments and delays the kinetics of dark adaptation through modulation of calcium homeostasis.
Journal of Biological Chemistry 06/2005; 280(21):20413-20. · 4.77 Impact Factor
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ABSTRACT: Sterol regulatory element-binding proteins (SREBPs) enhance transcription of genes encoding all of the proteins required for the cellular synthesis and uptake of cholesterol and unsaturated fatty acids. Here, we use suppression subtractive hybridization to identify a previously unrecognized SREBP-enhanced gene in mice. The gene encodes a membrane-bound enzyme that we designate SCALD, for short-chain aldehyde reductase. We expressed SCALD in bacteria, purified it extensively, and studied its catalytic properties in detergent solution. The enzyme specifically uses NADPH to reduce a variety of short-chain aldehydes, including nonanal and 4-hydroxy-2-nonenal. The enzyme also reduces retinaldehydes, showing equal activity for all-trans-retinal and 9-cis-retinal. Northern blot analysis indicates that SCALD is expressed most abundantly in mouse liver and testis. In the liver of mice, SCALD is suppressed by fasting and induced by refeeding, consistent with regulation by SREBPs. In testis, SCALD expression is restricted to pachytene spermatocytes, as revealed by visualization of mRNA and protein. SCALD is also expressed in four layers of the retina, including the outer segment of rods and cones, as revealed by immunohistochemistry. SCALD appears to be the mouse ortholog of the human protein that has been designated variously as prostate short-chain dehydrogenase/reductase 1, retinal reductase 1, and retinol dehydrogenase 11. In view of its ability to reduce short-chain aldehydes in addition to retinals, we propose that SCALD may be induced by SREBP in liver and other tissues to prevent toxicity from fatty aldehydes that are generated from oxidation of unsaturated fatty acids that are synthesized as a result of SREBP activity.
Journal of Biological Chemistry 09/2003; 278(34):32380-9. · 4.77 Impact Factor
