Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An abortive infection of a rabbit cornea cell line (RC-60) by vesicular stomatitis virus (VSV), yielding less than 1 PFU/cell, was converted to a productive infection, yielding 1,900 PFU/cell, when cells were superinfected with vaccinia. Studies on the synthesis of VSV-directed RNA in RC-60 cells suggest that the abortive infection by VSV alone may be due in part to (i) a limited production of 40S virion RNA and (ii) a markedly reduced activity of virion-bound transcriptase activity in RC-60 cells compared to the activity in mouse L cells, a permissive host for VSV. No recognizable VSV structures, except a small amount of viral core structures, were produced by the abortive infection. In contrast, double infection of RC-60 cells with VSV and vaccinia in the presence of hydroxyurea resulted in the production of infective B particles of VSV. Although the function supplied by vaccinia responsible for the productive replication of VSV in double infected RC-60 cells has not been identified, metabolic inhibitor studies indicate that continuous vaccinia-dependent RNA synthesis is required for maximal production of infective VSV. The possibility is considered that vaccinia may supply a product or function required for VSV replication which is ordinarily supplied by the host but which is lacking in RC-60 cells.
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PMID:Abortive infection of a rabbit cornea cell line by vesicular stomatitis virus: conversion to productive infection by superinfection with vaccinia virus. 16 5

Experimental models and clinical investigations have suggested that epidermal growth factor (EGF) may have a role in corneal wound healing. It has been identified as a normal component of human tears. Rabbit and mouse lacrimal glands have recently been shown to synthesize EGF messenger RNA (mRNA). The purpose of the present study was to determine whether the human lacrimal gland synthesizes EGF mRNA. Total cellular RNA was isolated from pathologic specimens of normal human lacrimal glands from two individuals. Reverse transcriptase was used to generate complementary DNA (cDNA) using a human EGF-specific mRNA primer. Amplification of EGF-related cDNA sequences was performed with the polymerase chain reaction (PCR) and human EGF-derived up- and downstream primers. The PCR products from both lacrimal glands contained an amplified product of the expected length of approximately 410 base pairs. The PCR-generated fragment was verified as an EGF-related amplification product with Southern blotting using a synthetic oligonucleotide probe derived from the mature coding sequence of EGF. These results conclusively demonstrate that the human lacrimal gland synthesizes EGF and suggest that the lacrimal gland could have a regulatory role in maintaining the ocular surface and possibly regulating corneal wound healing through the secretion of EGF.
Cornea 1991 Nov
PMID:Epidermal growth factor messenger RNA production in human lacrimal gland. 172 72

Patients undergoing penetrating keratoplasty for prior herpes simplex keratitis (group A) and corneal disease unrelated to herpes simplex (group B) were investigated to assess whether the cornea is a site for herpes simplex viral latency. All patients were seropositive for herpes simplex viral antibody. Virus was isolated from the tear film postoperatively in one patient and on cocultivation from the cornea of another patient. Herpes simplex viral DNA, however, was detected in the corneas of all patients from group A and half of those from group B by means of the polymerase chain reaction and primers to three well separated regions of the viral genome. Three donor corneas had no evidence of herpes simplex viral DNA. Using RNA polymerase chain reaction, we found evidence of a latency associated transcript and also that of a glycoprotein C coding transcript in two corneas, indicating viral replication. Nine corneas had evidence of a latency associated transcript but no glycoprotein C transcript, which suggests that herpes simplex virus may be maintained in a latent state in the corneas of patients with prior herpes simplex keratitis and in some patients with corneal disease unrelated to the herpes simplex virus.
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PMID:Evidence for herpes simplex viral latency in the human cornea. 185 Jun 15

Interleukin-1 receptor antagonist (IL-1ra) is an important modulator of IL-1 activity in a variety of tissues. IL-1ra is differentially produced by different cell types as a 22-26-kD secreted peptide (sIL-1ra) and/or a smaller 16- or 18-kD intracellular peptide (icIL-1ra). This study was undertaken to evaluate the production of IL-1ra in the human cornea. IL-1ra mRNA can be detected in early passage human corneal epithelial cells and corneal stromal fibroblasts and is significantly enhanced by IL-1. Corneal endothelial cells do not express IL-1ra mRNA. Immunohistochemical studies of cultured corneal cells and whole human cornea demonstrate IL-1ra protein production by both the epithelial and stromal cells but not the endothelial cells. Reverse transcriptase polymerase chain reaction, ELISA, and immunoprecipitation studies indicate that corneal epithelial cells are capable of producing both icIL-1ra and sIL-1ra forms of IL-1ra whereas the corneal stromal cells produce only icIL-1ra. In addition to the larger 18-kD icIL-1ra, both corneal epithelial and stromal cells are also capable of producing a smaller recently described 16-kD icIL-1ra. Thus, the differential production of IL-1ra in the human cornea is unique; whereas both epithelial and stromal cells produce icIL-1ra (type 1 and type 2), the epithelial cells appear to also produce sIL-1ra. It is proposed that these IL-1ra proteins may play an important role in regulating IL-1-induced corneal inflammation.
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PMID:Novel production of interleukin-1 receptor antagonist peptides in normal human cornea. 781 49

The human gene for the seventh largest subunit of RNA polymerase II complex, hsRPB7 was cloned, sequenced and mapped. This complex is an integral part of the transcription-coupled DNA repair mechanism and has been shown to be involved in several human genetic diseases and implicated in many others. The hsRPB7 gene consists of 8 exons and spans approximately 5.1 kb. Southern blots of genomic and cloned DNA suggest that hsRPB7 is coded for by a single gene. Using human radiation hybrids and YACs, the gene was localized to 11q13.1, within 70 kb of marker D11S1765. The sequence of the 5' flanking region does not contain a TATA element, but does contain several Sp1 binding sites, an AP-1 site and a novel inverted polymorphic GATA tandem repeat. This novel GATA repeat can be used for linkage analysis. The hsRPB7 gene seems to be highly conserved among eukaryotic species, showing general sequence conservation to yeast and Drosophila. Northern blot analysis reveals a high degree of tissue-specific expression. For example, adult retina, brain and kidney exhibit a relatively high level of expression. A moderate level of expression is observed in heart, lung, testis, cornea, retinal pigmented epithelium/choroid and placenta with a lower level of expression in the uterus, small intestine and skeletal muscle. A very low level of expression was observed in stomach and liver. Comparison between four fetal and adult tissues also demonstrate a surprising level of developmental specificity. Expression in fetal retina is considerably lower than fetal brain but similar to adult retina.
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PMID:Human gene for the RNA polymerase II seventh subunit (hsRPB7): structure, expression and chromosomal localization. 925 63

Members of the thrombospondin (TSP) family of proteins have been implicated in wound healing. The cells of the corneal stroma (keratocytes) are capable of synthesising TSP-1 in a wound repair phenotype, but do not appear to produce the protein in the normal human adult cornea. We employed reverse-transcriptase polymerase chain reaction (RT-PCR) to determine whether human corneal stromal cells can express TSPs other than TSP-1. Cultured keratocytes contained messenger RNA (mRNA) for TSP-2 and TSP-3 (in addition to TSP-1), but not for TSP-4 or cartilage oligomeric matrix protein (COMP; TSP-5). Keratocytes in the normal cornea contained mRNA for TSP-1 but not for other TSPs. The distribution of keratocyte TSP-2 and TSP-3 immunoreactivity had some similarities to that of TSP-1 and, like TSP-1, neither protein could be detected in the cells of the normal corneal stroma. The observations suggest that keratocytes in wound repair phenotype produce TSP-2 and TSP-3 in addition to TSP-1. TSPs may play a pivotal role in corneal stromal repair and, since TSP-1 and TSP-2 have anti-angiogenic properties, may also have a function in regulating the avascularity of the central cornea.
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PMID:Corneal stromal cells (keratocytes) express thrombospondins 2 and 3 in wound repair phenotype. 1194 89

The expression of vascular endothelial growth factor has been strongly implicated in the pathogenesis of conditions leading to inappropriate blood vessel growth in the eye. As such, vascular endothelial growth factor is an attractive target for anti-angiogenic therapies designed to treat neovascular eye diseases. One such therapy, antisense gene therapy, is a technique based on the ability of single-stranded DNA or RNA sequences to alter the expression of targeted genes. Recombinant adenoviruses have demonstrated efficient ocular cell transduction with a high level of transgene production. Cauterization of the normally avascular rat cornea results in a strong neovascular response, making it an ideal animal model for the testing of anti-angiogenic therapies. In this study, a recombinant adenovirus system was assessed for the ability to express biologically relevant antisense RNA to reduce vascular endothelial growth factor expression in a rat model of corneal neovascularization. Recombinant adenovirus constructs expressing short and long antisense and sense vascular endothelial growth factor cDNA, under the control of cytomegalovirus major immediate early promoter or the RNA polymerase III promoter, VA1, were constructed. The expression of short and long antisense RNAs was demonstrated by Northern blot hybridization. All constructs were capable of producing RNA, and the highest level of antisense RNA production was detected in retinal pigment epithelial cells which had been transduced with the longer antisense cDNA construct under the control of the VA1 promoter. This construct was also the most efficient in reducing in vitro vascular endothelial growth factor production (P<0.05) and human endothelial cell proliferation. This construct was subsequently injected into rat eyes 24hr prior to cauterization of the cornea and antisense vascular endothelial growth factor expression was demonstrated by in situ hybridization. The resulting neovascular response was clearly inhibited at 4, 7 and 14 days post-cautery, compared to the control injections which demonstrated an intense neovascular response. Only one out of six eyes injected with the long antisense cDNA construct under the control of the VA1 promoter demonstrated any vascular response to cautery. The reduction in the neovascular response was correlated, with significantly lower amounts of vascular endothelial growth factor protein in the corneas (P=0.006). These observations suggest that the specific down-regulation of vascular endothelial growth factor production is sufficient to reduce the corneal neovascular response and that recombinant adenovirus might be a useful vehicle to produce antisense RNA in situ to down-regulate ocular gene expression.
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PMID:Inhibition of corneal neovascularization by recombinant adenovirus mediated antisense VEGF RNA. 1247 Sep 64

At least two cellular processes are required for corneal epithelium homeostasis and wound repair: cell proliferation and cell-cell adhesion. These processes are delicately balanced to ensure the maintenance of normal epithelial function. During wound healing, these processes must be reprogrammed in coordination to achieve a rapid re-epithelialization. Basonuclin (Bnc1) is a cell-type-specific transcription factor expressed mainly in the proliferative keratinocytes of stratified epithelium (e.g., corneal epithelium, epidermis and esophageal epithelium) and the gametogenic cells in testis and ovary. Our previous work suggested that basonuclin could regulate transcription of ribosomal RNA genes (rDNA) and genes involved in chromatin structure, transcription regulation, cell-cell junction/communication, ion-channels and intracelllular transportation. However, basonuclin's role in keratinocytes has not been demonstrated in vivo. Here we show that basonuclin-null mutation disrupts corneal epithelium homeostasis and delays wound healing by impairing cell proliferation. In basonuclin-null cornea epithelium, RNA polymerase I (Pol I) transcription is perturbed. This perturbation is unique because it affects transcripts from a subset of rDNA. Basonuclin-null mutation also perturbs RNA polymerase II (Pol II) transcripts from genes encoding chromatin structure proteins histone 3 and HMG2, transcription factor Gli2, gap-junction protein connexin 43 and adheren E-cadherin. In most cases, a concerted change in mRNA and protein level is observed. However, for E-cadherin, despite a notable increase in its mRNA level, its protein level was reduced. In conclusion, our study establishes basonuclin as a regulator of corneal epithelium homeostasis and maintenance. Basonuclin likely coordinates functions of a subset of ribosomal RNA genes (rDNA) and a group of protein coding genes in cellular processes critical for the regulation of cell proliferation.
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PMID:Basonuclin-null mutation impairs homeostasis and wound repair in mouse corneal epithelium. 1797 52

In species of the frog genus Xenopus, lens regeneration occurs through a process of transdifferentiation, in which cornea epithelial cells presumably undergo dedifferentiation and subsequently redifferentiate to form a new lens. Experimental studies have shown that the retina provides the key signal required to trigger this process once the original lens is removed. A previous study showed that addition of an exogenous fibroblast growth factor (i.e., FGF1 protein) could initiate transdifferentiation of cornea epithelial cells in culture. To determine the role of FGF signaling in X. laevis lens regeneration, we have examined the presence of specific FGFs and their receptors (FGFRs) during this process and evaluated the necessity of FGFR signaling. Reverse transcriptase-polymerase chain reaction analyses reveal that a number of FGF family members are expressed in cornea epithelium and retinal tissues both before and during the process of lens regeneration. Of these, FGF1, FGF8, and FGF9 are expressed principally in retinal tissue and not in the cornea epithelium. Hence, these ligands could represent key signaling factors originating from the retina that trigger regeneration. The results of experiments using an in vitro eye culture system and an FGFR inhibitor (SU5402) suggest that FGFR signaling is required for lens regeneration in Xenopus.
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PMID:FGF signaling is required for lens regeneration in Xenopus laevis. 2187 16

Hexagonal-shaped human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na(+)- and K(+)-dependent ATPase (Na(+)/K(+)-ATPase). Because HCEC proliferative activity is low in vivo, once HCEC are damaged and their numbers decrease, the cornea begins to show opacity due to overhydration, resulting in loss of vision. HCEC cell cycle arrest occurs at the G1 phase and is partly regulated by cyclin-dependent kinase inhibitors (CKIs) in the Rb pathway (p16-CDK4/CyclinD1-pRb). In this study, we tried to activate proliferation of HCEC by inhibiting CKIs. Retroviral transduction was used to generate two new HCEC lines: transduced human corneal endothelial cell by human papillomavirus type E6/E7 (THCEC (E6/E7)) and transduced human corneal endothelial cell by Cdk4R24C/CyclinD1 (THCEH (Cyclin)). Reverse transcriptase polymerase chain reaction analysis of gene expression revealed little difference between THCEC (E6/E7), THCEH (Cyclin) and non-transduced HCEC, but cell cycle-related genes were up-regulated in THCEC (E6/E7) and THCEH (Cyclin). THCEH (Cyclin) expressed intercellular molecules including ZO-1 and N-cadherin and showed similar Na(+)/K(+)-ATPase pump function to HCEC, which was not demonstrated in THCEC (E6/E7). This study shows that HCEC cell cycle activation can be achieved by inhibiting CKIs even while maintaining critical pump function and morphology.
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PMID:Establishment of functioning human corneal endothelial cell line with high growth potential. 2227 23


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