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)

The outer cornea of larval Xenopus laevis can reprogram cell differentiation when cultured in medium conditioned by X. laevis neural retina (XRCM) or by Rana esculenta neural retina (RRCM). Under these experimental conditions corneal cells showed the same series of cytological changes of fibre cell differentiation observed during ontogenesis and in vivo lens regeneration: enlargement of nuclei and nucleoli, increase of ribosomal population (cytoplasm-basophilia), cell elongation gradual loss of basophilic properties and acquisition of acidophilic properties for crystallin synthesis and accumulation. These events were completely dependent on XRCM or RRCM, suggesting that the neural retina secretes a factor(s) which initiates and sustains lens fibre transdifferentiation of the corneal epithelial cells. This culture system appears to be a suitable one for investigating the control of lens fibre transdifferentiation in vitro.
Cell Mol Life Sci 1997 Dec
PMID:Lens fibre transdifferentiation in cultured larval Xenopus laevis outer cornea under the influence of neural retina-conditioned medium. 944 44

The human ALDH3 gene is constitutively expressed in stomach, lung, esophagus, and cornea, but hardly detectable in the normal liver. However, it is highly activated in the hepatocellular carcinoma tissues from approximately 50% of patients. The nuclear DNA binding factors exist in both ALDH3-positive cancerous liver and ALDH3-positive HepG2 cells, but not in ALDH3-negative Hep3B cells and normal liver tissues. South-western blot hybridization showed the existence of two nuclear-binding protein components, 35 and 14 kDa, in ALDH3-positive cancerous liver tissues. These two DNA binding proteins were not found in normal stomach tissues and stomach carcinoma KATO III cells. DNaseI footprint analysis identified two protective regions within the ALDH3 promoter. The first protected region has one putative CCAAT-box and one putative Sp1-site. The second protected region contains a putative HiNF-A binding sequence. These findings suggest that a high level of expression of ALDH3 in cancerous liver tissues resulted from the expression or activation of at least two nuclear proteins reacting to the ALDH3 promoter region.
Int J Mol Med 1998 Sep
PMID:Expression of human aldehyde dehydrogenase-3 associated with hepatocellular carcinoma: promoter regions and nuclear protein factors related to the expression. 985 7

P53 is a transcription factor that has been found to be expressed in association with cell proliferation and apoptosis. Previously, bacterial chloramphenicol acetyl transferase (CAT) enzymatic expression was predominantly found in the testes of p53 promoter driven-CAT transgenic mice. In the current study, we extended this study to survey p53 expression across both the central and peripheral nervous systems of the same strain of transgenic mice as well as their parental strain. High levels of p53 promoter driven-CAT activity was observed in the cerebellum, hippocampus, hypothalamus, pons, thalamus and upper cerebral spine. Furthermore, we consistently found unexpectedly high levels of p53 promoter-driven CAT expression in the eyes. These observations were reinforced by p53 protein analysis using a p53 pan ELISA assay. Immunohistochemical studies confirmed and further defined p53 expression in several regions of the nervous system. Significantly, p53 promoter-driven CAT expression was visualized in the Ammon horn of the hippocampus, in the Purkinje cells of the cerebellum and in the cornea as well as in the retina of the eye. Furthermore, strong p53 protein expression was found in the cornea of the parental mouse strain. p53 ELISA demonstrated a profile of p53 protein concentration, which correlate well with the high p53 promoter-driven CAT activities observed in the cerebellum, hindbrain, hypothalamus, thalamus, hippocampus, whole eyes as well as with the low CAT activities observed in the cortex and spinal cord. In both of these assays considerable p53 promoter activity and p53 protein levels were found in post-mitotic non-dividing cells.
Brain Res Mol Brain Res 1999 Sep 08
PMID:Tissue-specific p53 expression in the nervous system. 1052 97

Studies describe an attenuation of sugar cataract formation by topical administration of ethyl pyruvate. Cataract formation was induced by feeding young rats a 30% galactose diet. Mature cataracts appeared in about thirty days. Instillation of the eye drops containing 5% ethyl pyruvate decelerated the process significantly. Biochemically, the effect was reflected by lowering in the contents of dulcitol and glycated proteins. The ATP levels were also higher in comparison to the placebo treated group. The effects are hence attributable to the effect of pyruvate in inhibiting dulcitol synthesis and protein glycation, in addition to its antioxidant properties and metabolic support. The use of esterified pyruvate instead of the unesterified pyruvate was preferred because of its greater penetration through the cornea and consequently a higher concentration attained in the aqueous humor.
Mol Cell Biochem 1999 Oct
PMID:Attenuation of sugar cataract by ethyl pyruvate. 1056 89

Angiostatin is a potent angiogenesis inhibitor that is composed of the first four kringles of plasminogen fragment. Angiostatin with one less kringle molecule (kringle 1 to 3) was recently demonstrated to be an effective angiogenic inhibitor. To determine whether recombinant plasminogen kringle 1-3 (rPK1-3) can inhibit the corneal neovascularization induced by potent angiogenic factors; angiogenin, bFGF, or VEGF, hydron polymer discs each containing 2.0 microg of angiogenin, 500 ng of bFGF, or 500 ng of VEGF respectively were implanted into the corneal stroma of 138 rabbit eyes, and then discs each containing 10 microg, 12.5 microg, 20 microg or 30 microg of rPK1-3 were implanted randomly. Discs containing phosphate buffered saline were also implanted as a control. The angiogenesis score on number and length of newly formed vessels on the each of the rabbit's cornea were recorded daily by two observers (blinded). The treated corneas were also examined histologically. Recombinant PK1-3 treated corneas showed less neovascularization induced by all angiogenic factors (p < 0.05). and the extent of inhibition of neovascularization was proportional to the concentration of rPK1-3 (p < 0.05). Histologic examination showed leukocyte infiltration into the corneal stroma on the PBS treated eyes whereas rPK1-3 treated eyes showed only traces of leukocytes. These results of the effective rPK1-3 inhibition of corneal neovascularization induced by angiogenin, bFGF, or VEGF suggest that this angiostatin related fragment, rPK1-3, may be useful in the treatment of various neovascular diseases.
Exp Mol Med 1999 Dec 31
PMID:The inhibitory effects of recombinant plasminogen kringle 1-3 on the neovascularization of rabbit cornea induced by angiogenin, bFGF, and VEGF. 1063 Mar 75

The Rx and pax6 homeobox genes are among the earliest genes expressed in the eye primordia and play crucial roles in the specification of ocular fate. These genes exhibit strong conservation of sequence and expression patterns among vertebrates. As transcription factors, Rx and Pax6 exert their effects through the activation and repression of downstream targets. Overexpression of each protein induces ectopic retinal tissue formation, as well as induction of the other. pax6 gene mutations have been correlated with an array of human diseases, and a similar array of mutations potentially exists for the human Rx gene. Based on functional studies, the vertebrate Rx and pax6 genes are likely to regulate cell proliferation and are required for the initial commitment to retinal and lens cell fate, respectively, while pax6 appears to play additional roles in the formation of the retina and cornea.
Cell Mol Life Sci 2000 Feb
PMID:Regulation of eye formation by the Rx and pax6 homeobox genes. 1076 16

Recent investigations show that glycosaminoglycans (GAGs) and proteoglycans (PGs) have the ability to affect lipid peroxidation, one the best characterized forms of free radical mediated biological damage. A protective effect of these extracellular matrix (ECM) components has been demonstrated in various experimental systems, including fatty acids and liposomes, where oxidation was induced by transition metals, including copper and iron. The effect was specific and dependent on the type and structural features of GAGs and PGs. The mechanism of peroxidation inhibition was likely to be dependent, at least to a large extent, on the sequestration of transition metals by GAG chains. Thus, it is conceivable that GAGs in the ECM and in the pericellular space may contribute to protecting cells against free radical damage. It is of particular interest that in certain tissues (cornea and aorta) aging was associated with a decrease of content of the GAGs which were most effective as anti-oxidant. This suggests that age-induced modifications of ECM composition in certain tissues may increase the susceptibility to oxidative stress. The investigation on the effect of GAGs on lipoprotein oxidation led to apparently conflicting results. An interesting reconciliation is possible, according to which GAGs exerted their protective effect under experimental conditions not compatible with the formation of lipoprotein-GAG complexes; rather, lipoproteins exhibited increased susceptibility to metal-catalyzed oxidation (MCO), possibly due to structural modifications of the particle after binding to GAGs or PGs. This process is likely to occur in the intimal matrix of arteries.
Int J Mol Med 2000 Aug
PMID:The effect of glycosaminoglycans and proteoglycans on lipid peroxidation. 1089 55

1. The aim of this study was to determine the epithelial changes of the conjunctiva and cornea up to 7 days after corneal debridement and the changes highlighted included (1) proliferation, (2) production of growth factor, (3) changes in calcium binding protein marker, (4) production of cytokine, and (5) maturity of the regeneration corneal epithelium. 2. The cytochemical changes of the corneal and conjunctival epithelia of rabbit were analyzed up to 7 days after debridement. 3. An increase in proliferating cell nuclear antigen (PCNA) was observed in the limbal epithelia 12 hr after lesion and reached a peak by 48 hr. 4. Some proliferating limbal cells also contained epidermal growth factor (EGF) beginning 24 hr after injury. The early limbal cell proliferation and the EGF production and their persistence until 7 days after lesion were likely involved with the process of regeneration. 5. Other positive markers appeared after lesion included tumor necrosis factor (TNFalpha) and calcium binding proteins S100A and S100B, which appeared mainly within the first 48 hr after lesion and then started to decline. The short appearance and the relatively small quantity of TNFalpha indicated that this cytokine was probably not very important in the repair process and its appearance might be related to the injury induced. The presence of S100A and S100B could be associated with both cell death after injury and the proliferation of new epithelium. 6. The cornea epithelium was still immature 7 days after lesion in that it still contained cytokeratin. 7. In conclusion, the critical hours of peak conjunctival and corneal changes after corneal debridement were in the first 2 days.
Cell Mol Neurobiol 2000 Aug
PMID:Changes of cytochemical markers in the conjunctival and corneal epithelium after corneal debridement. 1090 Dec 67

Although renal disease is the most prominent feature of the lysosomal storage disease cystinosis, corneal cystine crystal formation remains a major complication, leading to photophobia, corneal erosions, and keratopathies. Moreover, the extent of corneal crystal accumulation reflects the course and severity of the disease itself, and the cornea is accessible to direct examination. Therefore, we employed a scoring system, based on a library of slit-lamp photographs of corneas with increasing crystal densities (0.00-3.00), to assess the degree of crystal accumulation in 170 patients with nephropathic cystinosis examined at the National Institutes of Health between 1976 and 2000. None of the patients had received topical cystine-depleting therapy at the time of the evaluation. In this natural history study, infants in the first year of life had absent or minimal corneal crystals, i.e., a corneal cystine crystal score (CCCS) of 0 or 0.25. However, the CCCS increased linearly with age, such that every patient had visible crystals by 16 months of age, and plateaued at approximately 3.00 by early adolescence. Longitudinal studies in representative patients support the cross-sectional results. Individuals homozygous for the common 57-kb deletion involving the cystinosis gene (CTNS) displayed the same course of corneal crystal accumulation as did individuals not bearing the large deletion. Patients with ocular or nonnephropathic cystinosis had CCCSs that were, in general, half those expected for patients with nephropathic cystinosis of the same age. Administration of 0.55% cysteamine eyedrops, given 6 to 12 times per day, dissolved corneal cystine crystals in 10 representative patients with nephropathic cystinosis aged 1 to 32 years within 8 to 41 months.
Mol Genet Metab
PMID:Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. 1100 3

11beta-hydroxysteroid dehydrogenase (11beta-HSD) regulates local actions of corticosteroids at glucocorticoid and mineralocorticoid receptors. Corticosteroids are thought to play important roles in ocular function. However, mechanisms of intraocular corticosteroid action are still unclear. Therefore, in this study, we examined the immunohistochemical localization of 11beta-HSD type 1 (11beta-HSD1), 11beta-HSD type 2 (11beta-HSD2), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in human ocular tissues from patients (6 months to 78 years of age; n = 10) retrieved from surgical pathology files. Both 11beta-HSD2 and MR immunoreactivity was detected only in non-pigmented epithelium of the ciliary body, but was undetectable in cornea, lens, iris, retina, choroid and sclera, in all the cases examined. GR was detected in all cell types in the human eye. 11beta-HSD1 immunoreactivity was not detected in the human eye in this study. These results suggest that 11beta-HSD2 play an important role in human ocular mineralocorticoid action, such as the production of aqueous humor, in the ciliary body. The widespread expression of GR suggests that glucocorticoids may play an important role in the function and homeostasis of the human eye.
Mol Cell Endocrinol 2001 Feb 28
PMID:Immunohistochemical distribution of 11beta-hydroxysteroid dehydrogenase in human eye. 1122 83


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