Редактирование: ABCA4 (раздел)

==Publications==

{{medline-entry
|title=Involvement of all-trans-retinal in acute light-induced retinopathy of mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19304658
|abstract=Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific [[ABCA4]] (ATP-binding cassette transporter 4) and [[RDH8]] (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration.
|mesh-terms=* ATP-Binding Cassette Transporters
* Acute Disease
* Aging
* Alcohol Oxidoreductases
* Animals
* Apoptosis
* Caspases
* Cell Line
* Cell Survival
* Chromatography, High Pressure Liquid
* Chromatography, Liquid
* Diterpenes
* Ethanolamine
* Humans
* Light
* Mass Spectrometry
* Mice
* Oxidation-Reduction
* Rats
* Retina
* Retinal Degeneration
* Retinal Diseases
* Retinaldehyde
* Retinyl Esters
* Rhodopsin
* Vitamin A
* bcl-2-Associated X Protein

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685698
}}
{{medline-entry
|title=Distinct spatio-temporal expression of ABCA and ABCG transporters in the developing and adult mouse brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16181433
|abstract=Using in situ hybridization for the mouse brain, we analyzed developmental changes in gene expression for the ATP-binding cassette (ABC) transporter subfamilies [[ABCA1]]-4 and 7, and [[ABCG1]], 2, 4, 5 and 8. In the embryonic brains, [[ABCA1]] and A7 were highly expressed in the ventricular (or germinal) zone, whereas [[ABCA2]], A3 and G4 were enriched in the mantle (or differentiating) zone. At the postnatal stages, [[ABCA1]] was detected in both the gray and white matter and in the choroid plexus. On the other hand, [[ABCA2]], A3 and A7 were distributed in the gray matter. In addition, marked up-regulation of [[ABCA2]] occurred in the white matter at 14 days-of-age when various myelin protein genes are known to be up-regulated. In marked contrast, [[ABCA4]] was selective to the choroid plexus throughout development. [[ABCG1]] was expressed in both the gray and white matters, whereas [[ABCG4]] was confined to the gray matter. [[ABCG2]] was diffusely and weakly detected throughout the brain at all stages examined. Immunohistochemistry of [[ABCG2]] showed its preferential expression on the luminal membrane of brain capillaries. Expression signals for [[ABCG5]] and G8 were barely detected at any stages. The distinct spatio-temporal expressions of individual ABCA and G transporters may reflect their distinct cellular expressions in the developing and adult brains, presumably, to regulate and maintain lipid homeostasis in the brain.
|mesh-terms=* ATP-Binding Cassette Transporters
* Aging
* Animals
* Animals, Newborn
* Brain
* Embryo, Mammalian
* Immunohistochemistry
* In Situ Hybridization
* Mice
* Mice, Inbred C57BL
* Tissue Distribution

|full-text-url=https://sci-hub.do/10.1111/j.1471-4159.2005.03369.x
}}
{{medline-entry
|title=Adenosine triphosphate-binding cassette transporter genes in ageing and age-related diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12437993
|abstract=The family of adenosine triphosphate (ATP)-binding cassette (ABC) transporters is the largest gene family known. While some ABC transporters translocate single substances across membranes with high specificity, others transport a wide variety of different lipophilic compounds. They are responsible for many physiological processes and are also implicated in a number of diseases. The present review focuses on ABC transporter genes which are involved in ageing and age-related diseases. Expression of [[ABCB1]] (MDR1, P-glycoprotein) increases with age in CD4( ) and CD8( ) T-lymphocytes indicating that P-glycoprotein may be involved in the secretion of cytokines, growth factors, and cytotoxic molecules. As T cells in aged individuals are hyporesponsive leading to a reduced immunodefence capability, a role of [[ABCB1]] in age-related immunological processes is presumed. The [[ABCA1]] (ABC1) gene product translocates intracellular cholesterol and phospholipids out of macrophages. Genetic aberrations in [[ABCA1]] cause perturbations in lipoprotein metabolism and contribute to atherosclerosis. [[ABCA4]] (ABCR) represents a retina-specific ABC transporter expressed in rod photoreceptor cells. The [[ABCA4]] gene product translocates retinyl-derivatives. Mutations in the [[ABCA4]] gene contribute to age-related macular degeneration. Polymorphisms in the sulfonylurea receptor gene (ABCC8, SUR1) are associated with non-insulin-dependent diabetes mellitus (NIDDM). Sulfonylureas inhibit potassium conductance and are used to treat NIDDM by stimulation of insulin secretion across ATP-sensitive potassium channels in pancreatic beta-cell membranes. Possible diagnostic and therapeutic implications of ABC transporters for age-related diseases are discussed.
|mesh-terms=* ATP-Binding Cassette Transporters
* Aging
* Animals
* Arteriosclerosis
* Diabetes Mellitus, Type 2
* Gene Expression Regulation
* Humans
* Macular Degeneration

|full-text-url=https://sci-hub.do/10.1016/s1568-1637(02)00046-6
}}
{{medline-entry
|title=A comprehensive survey of sequence variation in the [[ABCA4]] (ABCR) gene in Stargardt disease and age-related macular degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10958763
|abstract=Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter ([[ABCA4]]). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the [[ABCA4]] gene. In addition, we have assessed the proposed role for [[ABCA4]] in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.
|mesh-terms=* ATP-Binding Cassette Transporters
* Adolescent
* Adult
* Age of Onset
* Aged
* Aged, 80 and over
* Aging
* Alleles
* Child
* Child, Preschool
* Chromatography, High Pressure Liquid
* Chromosomes, Human
* Cohort Studies
* DNA Mutational Analysis
* Data Collection
* Exons
* Female
* Founder Effect
* Genes, Recessive
* Genetic Testing
* Genetic Variation
* Germany
* Homozygote
* Humans
* Introns
* Macular Degeneration
* Middle Aged
* Mutation
* Polymorphism, Single-Stranded Conformational
* RNA Splice Sites

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287885
}}