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 trabecular meshwork, a specialized tissue in the anterior chamber of the eye, plays a major role in the regulation of aqueous humor outflow. We studied the effects of ascorbic acid, a significant component in the aqueous humor, on gene expression of type I collagen in cultures of bovine trabecular meshwork cells. These cells were plated for 6 days, exposed to ascorbic acid in concentrations of 100, 250 and 500 micrograms/ml for 3 days and labeled with (3H)proline for the last 24 hrs. Cultures that did not receive ascorbic acid served as controls. Bacterial collagenase assays showed enhanced incorporation of (3H)proline into collagenous proteins in cultures treated with 100 and 250 micrograms/ml of ascorbic acid. Gel electrophoresis and fluorography revealed that ascorbic acid caused a 2.6- to 4.9-fold increase in production of alpha 1 (I) and alpha 2(I) collagen chains by trabecular meshwork cells. Such an increase was found, using a cDNA probe specific for pro alpha 1(I) chains, to be accompanied by an increase in steady-state mRNA levels. Similar findings were also yielded from in situ hybridization experiments. These results, coupled with previously demonstrated ascorbate-induced effects on glycosaminoglycan, fibronectin and laminin synthesis, suggest that ascorbic acid is a key mediator of the extracellular matrix production by trabecular meshwork cells. Fluctuations in its concentration may lead to alterations in the makeup and assembly of matrices underlying the cells.
Cell Mol Biol 1992 Sep
PMID:Ascorbic acid modulates collagen type I gene expression by cells from an eye tissue--trabecular meshwork. 130 7

The ocular pharmacokinetics of bendazac were studied in rabbits, following intravenous administration of bendazac lysine. The compound and its 5-hydroxyderivative were determined in different eye compartments and plasma by radioassay, using [14C]bendazac, and HPLC. The highest concentrations were found in the iris and in descending order in the ciliary body, retina, cornea, tears, aqueous humor, vitreous, and lens. The time course of concentrations in the plasma, aqueous and vitreous humor, ciliary body, and retina showed kinetics described by the exponential equation y = aebx with a half-life of 2.47, 4.56, 3.59, and 3.22 hr, respectively; in the lens the half-life was 17.77 hr.
Exp Mol Pathol 1985 Dec
PMID:Investigations on the ocular pharmacokinetics of bendazac in rabbits. 406 7

Flestolol, N(1,1-dimethyl-2-ureidocthyl)-2-hydroxy-3-(o-fluorobenzoyloxy++ +) propylamine, (F), is an ester containing an ultra short-acting beta blocker intended for the treatment of myocardial dysfunctions. In vitro incubation of F, procaine, chloroprocaine, and atropine with blood from different New Zealand White (NZW) rabbits resulted in a bimodal distribution (70% fast, 30% slow) of ester hydrolysis rates. Using F as a model substrate, bimodal hydrolysis rates were also observed in NZW rabbit cornea but not aqueous humor, iris-ciliary body complex and ocular tissues of pigmented rabbits. In addition, the bimodal distribution of esterase activity was not observed in blood from rats, dogs, and humans. Incubation of esters at various positions of the phenoxypropanolamine nucleus of beta blockers with NZW rabbit blood indicated structural specificity of the carboxylesterase in terms of unimodal or biomodal distribution of activity. These results strongly suggest that the carboxylesterase in NZW rabbit blood that hydrolyzes F and similar compounds is atropine esterase as described in the literature.
Res Commun Mol Pathol Pharmacol 1995 Apr
PMID:Polymorphic metabolism of flestolol and other ester containing compounds by a carboxylesterase in New Zealand white rabbit blood and cornea. 762 Aug 41

T1 alpha is the first marker gene known to be expressed in the adult lung solely by the alveolar type I epithelial cell. Previous studies showed that T1 alpha transcripts are abundant in early rat embryos where they are found in the nervous system and in the foregut and certain of its derivatives including the primitive lung. By mid- to late gestation T1 alpha messenger RNA (mRNA) expression is lost from neural tissues but appears to increase in the lung throughout fetal life. To determine whether the T1 alpha transcripts are translated into protein, especially in early embryos which sometimes express transcripts that are translationally silent, we performed immunohistochemistry on embryos and fetal tissues and analyzed certain tissues by western blotting using a monoclonal antibody against T1 alpha protein. T1 alpha protein is present at all sites that have previously been shown to express the mRNA and at similar developmental stages. As estimated from western blots, T1 alpha protein abundance peaks at about fetal day 16 in the brain and decreases thereafter to a relative level in the adult that is lower than that of the neural tube of the day 13 embryo. Relative protein abundance in the lung is very low, although detectable, on embryonic day 13 but increases slowly until fetal day 20 when there is a dramatic increase. At the time of birth, restriction to the type I cell is not complete and therefore must occur during postnatal lung development. Immunostaining reveals additional sites of expression in fetal and adult rats that had not been clearly visualized in previous in situ hybridization studies. T1 alpha is present in mesonephric tubules and apparently in primitive germ cells but is not detectable in specific cells in the adult kidney, ovary, or testis. However, cells of the choroid plexus of the central nervous system and the ciliary epithelium of the eye express T1 alpha in both fetuses and adults. The well-known functions of these epithelia are to elaborate cerebrospinal fluid and aqueous humor respectively by processes of active ion transport and water fluxes, probably through the aquaporin 1 (channel-forming integral membrane protein [CHIP] 28). We speculate therefore that T1 alpha protein may modulate or participate in these types of cellular functions in the lung.
Am J Respir Cell Mol Biol 1996 Jun
PMID:T1 alpha protein is developmentally regulated and expressed by alveolar type I cells, choroid plexus, and ciliary epithelia of adult rats. 865 86

Oxidative stress is thought to play a major role in cataract formation. The present experiments are aimed at gaining a better understanding of the systems that protect the lens from damage by reactive oxygen species. The aqueous humor normally contains hydrogen peroxide (H2O2), a compound capable of generating reactive oxygen species. The systems protecting the ocular lens from oxidative damage are primarily confined to the epithelium, a single layer of cells on the anterior side of the organ directly beneath the lens capsule. When cultured rabbit lenses were challenged with a single dose of 0.2 mM H2O2, cells in the peripheral region of the epithelium survived; those in the central region died. Here we investigate the histochemical and immunoperoxidase distributions of catalase, an enzyme which detoxifies H2O2, in cells from the peripheral and central regions of the epithelium on flat mount preparations of the epithelium. In a flat mount, the entire population of lens epithelial cells can be viewed on one preparation. The reaction product for catalase activity and its immunoperoxidase localization were more intense in peripheral epithelial cells than in cells throughout the central epithelium. Treatment of cultured lens epithelial cells or rabbit lenses with 3-aminotriazole or potassium cyanide, inhibitors of catalase, reduced or abolished the histochemical reaction product. Ultrastructural cytochemistry confirmed the presence of catalase in microperoxisomes of the epithelial cells from whole lenses. The decreased level of catalase throughout the central epithelium may account for the increased susceptibility of these cells to H2O2-induced cell death.
Cell Mol Biol (Noisy-le-grand) 1996 Mar
PMID:Regional differences in the distribution of catalase in the epithelium of the ocular lens. 869 57

Ocular toxicity of acetaminophen was investigated in cytochrome P450 inducer-responsive and nonresponsive strains of mice by light and electron microscopy. Acetaminophen injected into C57BL6 mice (responsive strain) that had been pretreated with beta-naphthoflavone produced cataract. The drug did not induce cataract in C57BL6 mice without the pretreatment or in DBA2 mice (nonresponsive strain) similarly pretreated with beta-naphthoflavone. Therefore, induction of cytochrome P450 enzymes that metabolically activate acetaminophen is essential for cataractogenesis. Following acetaminophen injection, tissue damage became noticeable first in the ciliary epithelium and then spread to the iris, corneal endothelium, and lens. The neural retina, retinal pigmented epithelium, and choroid remained unaffected. A close examination of tissues revealed that mitochondria are the primary target of acetaminophen cytotoxicity in ocular tissues affected. The nucleus, endoplasmic reticulum, and other subcellular structures appeared normal. The course of propagation of tissue damage and the almost exclusive damage to mitochondria suggest that the cytotoxic metabolite of acetaminophen is secreted with the aqueous humor by the ciliary epithelium and transported to the lens and that inhibition of mitochondrial energy metabolism, together with other effects of the metabolite, contributes to acetaminophen-induced cataract.
Exp Mol Pathol 1995 Oct
PMID:Histocytological study on the possible mechanism of acetaminophen cataractogenesis in mouse eye. 894 Oct 46

The trabecular meshwork (TM) is a specialized eye tissue essential for regulation of the aqueous humor outflow and control of the intraocular pressure. Disturbances of TM cells may lead to elevated intraocular pressure and glaucoma. This study assessed the dexamethasone effects on levels of extracellular matrix proteins and their integrin receptors in bovine TM cells. Instillation of glucocorticoids such as dexamethasone is known to result in ocular hypertension. The histologic changes induced resemble those seen in glaucoma. Examination of the effects of glucocorticoid therefore may provide insights into the pathogenesis of glaucoma. TM cells in either tissue culture or organ cultures were treated with 0 (control), 0.1, or 1 microM of dexamethasone for 72 h. Immunostaining, Western, Northern and dot blot analyses showed that dexamethasone caused an increase in levels of fibronectin and collagen type IV in tissue-cultured TM cells. Increased focal contacts were also observed but the levels of laminin and collagen type I were unaffected. The dexamethasone effect was similarly demonstrated in organ cultures, with the exception that collagen type I also was enhanced. These results suggest that dexamethasone modulates extracellular matrices in the TM. Glucocorticoid may exert its effect through such a modulation in the development of steroid glaucoma.
Int J Mol Med 1998 Feb
PMID:Glucocorticoid effects on extracellular matrix proteins and integrins in bovine trabecular meshwork cells in relation to glaucoma. 985 35

The MYOC (GLC1A) gene has recently been associated with both juvenile-onset primary open angle glaucoma (JOAG) and typical late-onset primary open angle glaucoma (POAG). As a result, much scrutiny has been focused on the pathology of these diseases. In order to better understand the pathophysiology of POAG, we have been developing a mouse model of the disease. As a step in this development, we have investigated the expression pattern of Myoc transcripts in embryonic and adult mouse tissue using Northern blot and in situ hybridization analyses. Myoc transcripts were found in high levels in adult eye, heart, brain, skeletal muscle and testis and to a lesser extent in lung and kidney. They were also present, albeit in very low amounts, during mouse embryogenesis. We present new evidence using in situ hybridization analysis that Myoc transcripts were present in widespread regions of the adult brain including the ependymal lining of the third and fourth ventricles, in the choroid plexus, the zonal layer of the junction of the inferior and superior colliculi, the neurons of the habenula, the piriform cortex, the median pre-optic nucleus of the hypothalamus, the olfactory tubercle, and in the inferior olive. In a functional sense, Myoc expression in the ependyma and choroid plexus, two regions of the brain involved in cerebrospinal fluid synthesis and resorption, parallels Myoc expression in the ciliary body and trabecular meshwork of the anterior segment of the eye where aqueous humor synthesis and outflow occur.
Brain Res Mol Brain Res 1999 May 07
PMID:Expression pattern and in situ localization of the mouse homologue of the human MYOC (GLC1A) gene in adult brain. 1032 Jul 84

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

Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway.
Hum Mol Genet 2001 Jan 15
PMID:Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor. 1115 59


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