Gene Expression of Proteases and Protease Inhibitors in the Human Ciliary Epithelium and ODM-2 Cells

Ortego, Javier; Escribano, Julio; Coca‐Prados, Miguel

doi:10.1006/exer.1997.0333

Cited by 27 publications

(17 citation statements)

References 36 publications

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“…Recently, cathepsin E has also been suggested to be specific in NT/NN processing (Kageyama et al, 1995), as well as the prohormone convertases PC1 and PC2 (Rovere et al, 1996). Now there exists evidence that the ocular cibiary epithelium expresses numerous proteases, including (1) cathepsin D (Ortego et al, 1997); (2) the neuropeptide-processing enzymes CPE and PAM (Ortego et al, 1996); and (3) the endopeptidases furin, PCi, and PC2 (this study). The latest finding is of particular interest because the coexpression of PCI and PC2 in the human cell line 0DM-2 could aid in the examination of the differential activation of these prohormone convertases, which results in distinct patterns of processing pro-NT/NN as described in the intestine and brain.…”

Section: Discussionmentioning

confidence: 51%

“…In view of these studies, it is unlikely that NT retains its biological activity in the aqueous humor, where numerous proteinases have been identified (Escribano et al, 1995;Ortego et al, 1996Ortego et al, , 1997. However, the possibility that NT might bind to a carrier protein in aqueous humor and be carried to a target tissue in the posterior chamber (i.e., lens) or anterior chamber (i.e., cornea endothelium and trabecular meshwork) cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Characterization and Differential Gene Induction of the Neuroendocrine‐Specific Genes Neurotensin, Neurotensin Receptor, PC1, PC2, and 7B2 in the Human Ocular Ciliary Epithelium

Ortego

Coca‐Prados

1997

Journal of Neurochemistry

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Abstract:The ocular ciliary epithelium is a bilayer of neuroepithelial cells specialized in the secretion of aqueous humor fluid and the regulation of intraocular pressure. In this study, we report on the expression of the regulatory peptide neurotensin (NT) and a set of differentiated neuroendocrine markers including neurotensin receptors (NTrs), the prohormone convertasesfurin, PCi, and PC2, and the neuroendocrine polypeptide 7B2 in the ciliary epithelium. Using a human cell line, ODM-2, derived from the nonpigmented ciliary epithelium, we demonstrate that (1) NT expression is highly activated by nerve growth factor, glucocorticoid, and activators of adenylate cyclase; (2) NTr expression is up-regulated by selective ligand-activated ,3 2-adrenergic receptor; and (3) PCi and PC2 expression are up-regulated via distinct signaling transduction pathways. PCi gene expression is activated by phorbol ester, and PC2 by the same inducers as those of NT expression. A radioimmunoassay for NT detected an NT-like immunoreactivity in human ciliary epithelium and ODM-2 cell extracts, in aqueous humor, and in conditioned culture medium. The results support the view that the entire ciliary epithelium functions as a neuroendocrine tissue, synthesizing, processing, and releasing NT into the aqueous humor where it may exert important physiological functions through autocrine and/or paracrine mechanisms.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Molecular Characterization and Differential Gene Induction of the Neuroendocrine‐Specific Genes Neurotensin, Neurotensin Receptor, PC1, PC2, and 7B2 in the Human Ocular Ciliary Epithelium

Ortego

Coca‐Prados

1997

Journal of Neurochemistry

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“…In this regard cathepsin D is considered one of the most important lysosomal enzymes in RPE cells (Regan et al, 1980;Rakoczy et al, 1997), and plays a major role in degradation of the phagocytosed photoreceptors during their renewal process (el-Hifnawi, 1995). Several reports have described cathepsin D in the adult RPE of mammals (Wilcox, 1988;Ortego et al, 1997;Yamada et al, 1990;Rakoczy et al, 1999;Frohlich and Klessen, 2001;Wasselius et al, 2003;Ahuja et al, 2008) and, in concordance with our findings, Hayasaka and Shiono (1982) showed that, with the exception of cathepsin D displaying high levels of activity, most of the lysosomal enzyme activities detected in the rabbit RPE were low at birth. A new question arises because we were able to detect the cathepsin D expression in the presumptive RPE from early embryonic stages, even before the morphological maturation of the first photoreceptor cells occurred, suggesting that this gene may be involved in the early differentiation of RPE cells.…”

Section: Spatiotemporal Expression Of Cathepsin B and D Genes: Relatimentioning

confidence: 99%

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

Bejarano-Escobar

Holguín-Arévalo

Montero

et al. 2011

Developmental Dynamics

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Here, we show a detailed chronotopographical analysis of cathepsin B and D expression during development of the mouse visual system. Both proteases were detected in large rounded/ameboid cells usually located in close relationship with prominent sites of extensive physiological cell death. In concordance with their morphological features and topographical distribution, we demonstrate that expressing cells corresponded with macrophages and microglial precursors. We found that as microglial precursors differentiated the expression of both cathepsins was down-regulated. Of interest, cathepsin B and D transcripts were never observed in degenerating cells. Our findings point to a role for cathepsin D and B in cell debris degradation after apoptotic processes rather than promoting cell death, as proposed for other developmental models. Additionally their pattern of expression suggests a role in the maturation of the microglial precursors.

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“…It is reasonable that other protease inhibitors identified here such as alpha-2-macroglobulin (A2M) and alpha-1-antichymotrypsin 1 and 2 could play similarly important roles. Moreover, many proteases and protease inhibitors are thought to be secreted by the ciliary epithelium, indicating that they could have a specific purpose in the AH [37]. Interestingly, A2M can inhibit proteases such as Cathepsin D, which we identified at a priority 2 level (not shown).…”

Section: Discussionmentioning

confidence: 77%

Multidimensional Protein Identification Technology

Berri-Trapero¹,

Villar-Moreno²

2006

Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine

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Aqueous humor (AH) supports avascular tissues in the anterior segment of the eye, maintains intraocular pressure, and potentially influences the pathogenesis of ocular diseases. Nevertheless, the AH proteome is still poorly defined despite several previous efforts, which were hindered by interfering high abundance proteins, inadequate animal models, and limited proteomic technologies. To facilitate future investigations into AH function, the AH proteome was extensively characterized using an advanced proteomic approach. Samples from patients undergoing cataract surgery were pooled and depleted of interfering abundant proteins and thereby divided into two fractions: albumin-bound and albumin-depleted. Multidimensional Protein Identification Technology (MudPIT) was utilized for each fraction; this incorporates strong cation exchange chromatography to reduce sample complexity before reversed-phase liquid chromatography and tandem mass spectrometric analysis. Twelve proteins had multi-peptide, high confidence identifications in the albumin-bound fraction and 50 proteins had multi-peptide, high confidence identifications in the albumin-depleted fraction. Gene ontological analyses were performed to determine which cellular components and functions were enriched. Many proteins were previously identified in the AH and for several their potential role in the AH has been investigated; however, the majority of identified proteins were novel and only speculative roles can be suggested. The AH was abundant in antioxidant and immunoregulatory proteins as well as anti-angiogenic proteins, which may be involved in maintaining the avascular tissues. This is the first known report to extensively characterize and describe the human AH proteome and lays the foundation for future work regarding its function in homeostatic and pathologic states.The aqueous humor (AH) is a clear fluid that fills the anterior segment of the eye and bathes the lens, iris, and corneal endothelium [1]. It is secreted by the ciliary body and functions to provide nutrients and remove waste from avascular tissues [2], as well as create the intraocular pressure that maintains the convex shape of the cornea. The AH has antioxidant properties and purported immune response roles during inflammation and infection [3,4]. However, the proteins that are responsible for carrying out these functions are largely unknown. The protein content of the AH has been studied extensively [5][6][7][8][9][10][11][12]; however, due to limitations in technology, an extensive and definitive description of human AH proteins has yet to be provided. Furthermore, proteins in the AH are thought to be involved in development of several eye diseases [13,14], and investigating the AH proteome will facilitate generation of new hypotheses regarding the etiology of such pathologies. Thus our goal in this study was to investigate the AH proteome and determine its protein constituents with high confidence using an advanced proteomic approach.

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Gene Expression of Proteases and Protease Inhibitors in the Human Ciliary Epithelium and ODM-2 Cells

Cited by 27 publications

References 36 publications

Molecular Characterization and Differential Gene Induction of the Neuroendocrine‐Specific Genes Neurotensin, Neurotensin Receptor, PC1, PC2, and 7B2 in the Human Ocular Ciliary Epithelium

Molecular Characterization and Differential Gene Induction of the Neuroendocrine‐Specific Genes Neurotensin, Neurotensin Receptor, PC1, PC2, and 7B2 in the Human Ocular Ciliary Epithelium

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

Multidimensional Protein Identification Technology

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