Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human corneal aldehyde dehydrogenase (designated ALDH3) was purified to homogeneity and characterised with respect to substrate specificity and inhibition by thiol reagents. The enzyme was present as a major soluble protein (5% of the total soluble protein) and was found to efficiently catalyse the oxidation of medium chain peroxidic aldehydes which may be found in the cornea. These findings are consistent with the proposal that ALDH3 plays a dual role in the absorption of UVR and in the oxidation of peroxidic aldehydes in the mammalian cornea. Disulfiram did not inhibit this enzyme under the conditions used in this study, however p-hydroxymercuribenzoate rapidly inactivated the enzyme. Analysis of the proteins of the cornea and surrounding tissue indicated that in both the cow and the human, changes in the nature and quantity of soluble proteins occurred. Phenotype variants of the ALDH3 were apparent in a small Australian population.
Biochem Mol Biol Int 1993 Sep
PMID:Human corneal aldehyde dehydrogenase: purification, kinetic characterisation and phenotypic variation. 826 Sep 46

The morphological change and DNA synthesis of the aging mice corneal cells were investigated by light microscopic radioautography after injection of tritiated thymidine. The result showed that the incorporation of tritiated thymidine in corneal cells changed with aging. The sites of tritiated thymidine incorporation were located in the epithelium from postnatal day 19 to 1 year after birth, in the stroma and endothelium from prenatal day 19 to postnatal day 8 only. The labeling index in the epithelial cells reached its highest value at 1 month after birth. Labelled stromal and endothelial cells reached their peaks simultaneously on the third day after birth and disappeared completely from postnatal 1 month onwards. The thickness of the cornea increased obviously at one month and there were no notable morphological change thereafter. Our investigation provides for the first time a systematic study on the age-related changes of DNA synthesis and construction in the aging mice corneas.
Cell Mol Biol (Noisy-le-grand) 1993 Jun
PMID:Light microscopic radioautographic study on DNA synthesis in aging mice corneas. 832 82

Murine corneal aldehyde dehydrogenase has been purified to homogeneity and characterized with a range of aldehyde substrates at pH 7.4. The enzyme was a dimer with a subunit molecular weight of 59 KDa. and appears to prefer aldehyde products of lipid peroxidation as substrates. The enzyme constituted approximately 5% of the total soluble protein of mouse cornea. A dual role has been proposed for corneal aldehyde dehydrogenase in providing the eye with protection against UV-B light: by oxidizing aldehydes generated through light-induced lipid peroxidation; and by the direct absorption of UV-B light by the enzyme.
Biochem Mol Biol Int 1993 Jul
PMID:Purification and properties of murine corneal aldehyde dehydrogenase. 840 11

Serine proteases play an important role in a diverse array of biological processes, including embryogenesis, metastasis, angiogenesis, thrombolysis and tissue invasion by certain parasites. The latter observation prompted us to explore the possibility that the tissue-invasive ocular parasite Acanthamoeba castellanii elaborates one or more serine proteases. Acanthamoeba sp. are pathogenic free-living amoebae that can produce an invasive, blinding inflammatory disease of the cornea, termed Acanthamoeba keratitis. The present study reports the preliminary purification and characterization of a novel plasminogen activator from an ocular isolate of A. castellanii. The parasite-derived enzyme has a molecular mass of approx. 40 kDa and produces a single band of lysis on fibrinogen-agarose zymographs. Activity of the enzyme is completely inhibited by treatment with diisopropylfluorophosphate, indicating that it is a serine protease. The parasite-derived serine protease is not inhibited by amiloride which is a strong inhibitor of urokinase-type plasminogen activator. Additionally, the enzyme is not inhibited by plasminogen activator inhibitor-1 which is the primary physiological inhibitor of both urokinase and tissue-type plasminogen activator. It does not cross-react with antibodies specific for human urokinase or tissue-type plasminogen activator. The parasite-derived enzyme activates plasminogen from several mammalian species, including human, cow and pig. Thus, it is possible that this parasite-derived serine protease contributes to the pathogenesis of Acanthamoeba keratitis.
Mol Biochem Parasitol 1995 Jul
PMID:Characterization of a plasminogen activator produced by Acanthamoeba castellanii. 857 23

Congenital heredity endothelial dystrophy (CHED) is a rare autosomal dominant disorder of the cornea. We have performed genetic linkage analysis with microsatellite markers on a seven generation British pedigree. Two-point linkage analysis revealed significant linkage of CHED (lod score >3) with seven marker loci mapping to chromosome 20. The highest observed lod score was 7.20 (theta=0.026) with marker D20S114. Multipoint analysis gave a maximum lod score of 9.34 between D20S48 and D20S471. This 2.7cM region lies within 30 cM region recently assigned to posterior polymorphous dystrophy (PPD). PPD and CHED may therefore be allelic, or alternatively it is possible that more than one gene in this region is responsible for these two corneal dystrophies.
Hum Mol Genet 1995 Dec
PMID:Linkage of congenital hereditary endothelial dystrophy to chromosome 20. 863 16

Several corneal complications have been reported in patients with long standing diabetes, but their exact pathogenesis is not well understood. It has been observed that the rate of epithelial wound healing in diabetic rats is delayed compared to those in normal animals. Here we present the effect of the free radial scavenger, Trolox, a water soluble vitamin E analogue, on epithelial wound healing in diabetic rat cornea. Three groups of rats were included: 1) normal, 2) diabetic, 3) diabetic + Trolox. After 3 months, rats were sacrificed and corneas removed. Standard 3 mm diameter corneal epithelial defects were made and residual epithelial defects were measured after 18 hours at 37 degrees C in a sterile cell culture incubator. Wound healing data measured in mm2 was used for statistical analysis. There were significantly larger (p < 0.05) epithelial defects in diabetic corneas as compared to control. Treatment with Trolox antioxidant in diabetic rats produced a significantly smaller (p < 0.05) epithelial defect than that of untreated diabetic rats. These studies suggest the involvement of free radicals in the delay of corneal epithelial wound healing in diabetes.
Res Commun Mol Pathol Pharmacol 1996 Jul
PMID:Acceleration of corneal wound healing in diabetic rats by the antioxidant trolox. 886 65

Schnyder's crystalline corneal dystrophy (SCCD) is an autosomal dominant eye disease characterized by a bilateral clouding of the central cornea, arcus lipoides and/or visible crystalline deposits of cholesterol in the stroma. There is accumulation of phospholipid, unesterified cholesterol and cholesterol ester in the corneal stroma; this is believed to be due to an imbalance in the local factors affecting lipid/cholesterol transport or metabolism. The cellular mechanism of abnormal lipid transport and metabolism in SCCD is of interest due to its potential involvement in atherosclerosis, and its implications for the pathogenesis of cerebrovascular, coronary and peripheral vascular disease as well as corneal opacification. To determine the chromosomal location of the SCCD locus, genome-wide linkage analysis has been performed in two large Swede-Finn kindreds recently identified in central Massachusetts. After analysing 300 microsatellite markers > 90% of the genome was excluded from linkage to the SCCD locus. We now report the chromosomal assignment of the gene for SCCD in both families to be 1p34.1-p36; the maximum multipoint lod-score was 8.48 in the interval between D1S214 and D1S503. From haplotype analysis, the SCCD locus lies in the 16 cM interval between markers D1S2663 and D1S228. Several candidate genes for SCCD have been localized to the 1p34.1-p36 interval.
Hum Mol Genet 1996 Oct
PMID:The gene for schnyder's crystalline corneal dystrophy maps to human chromosome 1p34.1-p36. 889 5

The corneal epithelium is known to have a rapid self-renewing capacity. The major advance in the field of corneal epithelial cell biology in the last decade is the establishment of the location of corneal epithelial stem cells at the limbus, i.e., the junctional zone between the cornea and the conjunctiva. This concept has helped explain several experimental and clinical paradoxes, produced a number of important clinical applications, and spawned many other research studies. This unique enrichment of epithelial stem cells at a site anatomically separated from their transient amplifying cells makes the ocular surface an ideal model to study the regulation of epithelial stem cells. The present review includes data from more recent studies and lays out other areas for future investigation, especially with respect to the role of apoptosis and cytokine dialogue between limbal epithelial stem cells and their stromal microenvironment.
Mol Biol Rep 1996
PMID:Regulation and clinical implications of corneal epithelial stem cells. 898 18

Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.
Mol Cell Biol 1997 Jul
PMID:Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. 919 36

Cat3vl and Cat3vao are two allelic, dominant cataract mutations that arose independently in the F1 generation after gamma-irradiation of male mice. The cataracts are already present at birth. Examination of the eyes with a slit lamp revealed completely vacuolated lenses in Cat3vl mutants and anteriorly located opacity in Cat3vao mutants. The appearance of the opacities does not differ between the individuals or between heterozygotes and homozygotes. Penetrance of the mutations is complete. Viability and fertility of the mutants are normal except in the case of the Cat3vl homozygotes. Cat3vao was assigned to the distal part of mouse chromosome 10, 3.2 +/- 0.9 cM away from the visible marker Steel (SlgbH). Using polymorphic markers the following locus order was found: D10Mit230-(0.2 +/- 0.1 cM)-Cat3vao-(2.5 +/- 0.6 cM)-D10Mit70. No recombinants were found between Cat3vao and the markers D10Mit4l and D10Mit95 among 921 offspring. The results exclude allelism of Cat3vao with CatLop or To2, which also map to chromosome 10. Candidate genes were tested by examination of their expression in the eye of newborn mice and by analysis of cDNA sequences. So far, negative results have been obtained for the genes encoding the proteoglycans lumican and decorin, the nuclear orphan receptor Tr2-11 and the transcription factor Elk3. Based on syntenic homology of the Cat3 region to the human chromosome 12q, the Cat3 mutants are discussed as mouse models for cornea plana congenita in man. The recovery of the Cat3 mutations demonstrates the importance of the corresponding locus for proper eye development.
Mol Gen Genet 1997 Dec
PMID:Cat3vl and Cat3vao cataract mutations on mouse chromosome 10: phenotypic characterization, linkage studies and analysis of candidate genes. 943 74


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