80 research outputs found
Transcriptomic Profiling Explains Racial Disparities in Pterygium Patients Treated With Doxycycline
No full textCitation: Larrayoz IM, RúaÓ, Velilla S, Martínez A. Transcriptomic profiling explains racial disparities on pterygium patients treated with doxycycline. Invest Ophthalmol Vis Sci
Estrogen reduces aldosterone, upregulates adrenal angiotensin II AT2 receptors and normalizes adrenomedullary Fra-2 in ovariectomized rats
No full textWe studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT 1 and AT 2 receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT 1 receptor expression in the adrenal zona glomerulosa and medulla, and decreased adrenomedullary catecholamine content and Fra-2 expression when compared to intact female rats. In the zona glomerulosa, estrogen replacement normalized AT 1 receptor expression,decreased AT 1B receptor mRNA, and increased AT 2 receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were:normalized AT 1 receptor expression, increased AT 2 receptor expression, AT 2 receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT 1 receptors, catecholamine synthesis and Fra-2 expression are partially under the control of reproductive hormones. Our results suggest that estrogen treatment decreases aldosterone production through AT 1 receptor downregulation and AT 2 receptor upregulation. AT 2 receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT 2 receptor upregulation and the decrease in AT 1 receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy.We studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT 1 and AT 2 receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT 1 receptor expression in the adrenal zona glomerulosa and medulla, and decreased adrenomedullary catecholamine content and Fra-2 expression when compared to intact female rats. In the zona glomerulosa, estrogen replacement normalized AT 1 receptor expression, decreased AT 1B receptor mRNA, and increased AT 2 receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were: normalized AT 1 receptor expression, increased AT 2 receptor expression, AT 2 receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT 1 receptors, catecholamine synthesis and Fra-2 expression are partially under the control of reproductive hormones. Our results suggest that estrogen treatment decreases aldosterone production through AT 1 receptor downregulation and AT 2 receptor upregulation. AT 2 receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT 2 receptor upregulation and the decrease in AT 1 receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy.Fil: Macova, Miroslava. National Institute of Mental Health. Department of Health and Human Services; Estados UnidosFil: Armando, Maria Ines. National Institute of Mental Health. Department of Health and Human Services; Estados UnidosFil: Zhou, Jin. National Institute of Mental Health. Department of Health and Human Services; Estados UnidosFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Tyurmin, Dmitri. National Institute of Mental Health. Department of Health and Human Services; Estados UnidosFil: Larrayoz Roldan, Ignacio M.. National Institute of Mental Health. Department of Health and Human Services; Estados UnidosFil: Saavedra, Juan M.. National Institute of Mental Health. Department of Health and Human Services; Estados Unido
Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration
No full textRetinoic acid regulates the human methionine sulfoxide reductase A (MSRA) gene via two distinct promoters
No full textAbstractMSRAs (methionine sulfoxide reductases A) are enzymes that reverse the effects of oxidative damage by reducing methionine sulfoxide back to methionine and recovering protein function. In this study we demonstrate that the transcriptional regulation of the human MSRA gene is complex and driven by two distinct promoters. Both promoters demonstrate high expression in human brain and kidney tissues. The upstream (promoter 1) regulates the msrA1 transcript that codes for the mitochondrial form of MSRA and is highly active in a broad range of cell lines. The downstream promoter (promoter 2) regulates the msrA2/3 transcripts that code for the cytosolic/nuclear forms of MSRA and is generally less active. Promoter 2 contains a 65 bp putative enhancer region that is very active in the retinal pigment epithelium-derived D407 cell line. Both promoters are partially regulated by all-trans retinoic acid via RARA and other RARs
Methylene Blue Prevents Retinal Damage Caused by Perinatal Asphyxia in the Rat
No full textPerinatal asphyxia (PA) is responsible for a large proportion of neonatal deaths and numerous neurological sequelae, including visual dysfunction and blindness. In PA, the retina is exposed to ischemia/reoxygenation, which results in nitric oxide (NO) overproduction and neurotoxicity. We hypothesized that methylene blue (MB), a guanylyl cyclase inhibitor, and free-radical scavenger currently used in the clinic, may block this pathway and prevent PA-induced retinal degeneration. Male rat pups were subjected to an experimental model of PA. Four groups were studied: normally delivered (CTL), normally delivered treated with 2 mg Kg-1 MB (MB), exposed to PA for 20 min at 37°C (PA), and exposed to PA and, then, treated with MB (PA-MB). Scotopic electroretinography performed 45 days after birth showed that PA animals had significant defects in the a- and b-waves and oscillatory potentials (OP). The same animals presented a significant increase in the thickness of the inner retina and a large number of TUNEL-positive cells. All these physiological and morphological parameters were significantly prevented by the treatment with MB. Gene expression analysis demonstrated significant increases in iNOS, MMP9, and VEGF in the eyes of PA animals, which were prevented by MB treatment. In conclusion, MB regulates key players of inflammation, matrix remodeling, gliosis, and angiogenesis in the eye and could be used as a treatment to prevent the deleterious visual consequences of PA. Given its safety profile and low cost, MB may be used clinically in places where alternative treatments may be unavailable.Fil: Fernandez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Peláez, Rafael. Centro de Investigación Biomédica de la Rioja ; EspañaFil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Soliño, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Contartese, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Dorfman, Verónica Berta. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Larrayoz, Ignacio M.. Centro de Investigación Biomédica de la Rioja ; EspañaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Martínez, Alfredo. Centro de Investigación Biomédica de la Rioja ; Españ
State-of-the-art of Heliostat Field Layout Algorithms and their Comparison
No full textAbstractIn this paper a complete review of the most relevant algorithms for the generation of heliostat field layouts is presented. For each of the reviewed algorithms, a description of the layout generation approach, all the input parameters required and the main formulation is provided. The algorithms have been compared for different scenarios covering a range of tower heights, heliostat sizes and acceptance angles (defining to what extent the resulting field is North configuration or surrounding). A robust methodology has been developed, which ensures a fair comparison of the algorithms by analysing the performance of optimized solar fields according to each layout generation method. For this, all the input parameters of each layout generation algorithm are optimized for each scenario prior to comparing the solar field performances. The main conclusion of the present study is that all the analysed layout generation algorithms lead to similar solar field efficiencies when compared for the considered scenarios once they are optimized. Further work is required to check if the algorithms also show similar efficiencies, or to what extent they are similar, when wider scenarios are considered (larger solar field powers, locations, etc.)
Adrenomedullin regulates club cell recovery following lung epithelial injury
No full textThe equilibrium between lung epithelium
damage and recovery in the context of chronic injury is
at the basis of numerous lung diseases, including lung
cancer and COPD. Understanding the contribution of
growth factors and other molecular intermediates to this
crosstalk may help in devising new therapeutic
approaches. To better understand the contribution of
adrenomedullin (AM) to lung homeostasis, we built club
cell-specific conditional knockout (KO) mice for AM
and subjected them to naphthalene injury. Untreated KO
mice had lower levels of club cell 10 KDa protein
(CC10) immunoreactivity than their wild type (WT)
littermates in both terminal and regular bronchioles.
Naphthalene injury resulted in a rapid necrosis of club
cells followed by a progressive recovery of the
epithelium. Club cells proliferated at higher rates in the
KO mice and at 21 days post-injury the club cell
coverage of the main bronchioles was higher and more
homogeneous than in the WT animals. In conclusion, the
paracrine/autocrine influence of AM in club cells subtly
modulates their proliferation and spreading kinetics
during lung epithelium recovery
Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization
No full text7-Ketocholesterol is present in lipid deposits in the primate retina: Potential implication in the induction of VEGF and CNV formation
No full textPURPOSE. 7-Ketocholesterol is a highly toxic oxysterol found in abundance in atherosclerotic plaques and is believed to play a critical role in atherosclerosis. The purpose of this study was to identify and localize 7-ketocholesterol (7kCh) in the primate retina and to examine the potential consequences of its presence in oxidized lipid deposits in the retina. METHODS. Unsterified 7kCh was identified and quantified by high-performance liquid chromatography-mass spectrometry. Localization of 7kCh was performed by immunohistochemistry. VEGF induction was determined by qRT-PCR. Cell viability was determined by measuring cellular dehydrogenase activity. Analyses were performed using ARPE19 and human vascular endothelial cells (HMVECs). RESULTS. 7-Ketocholesterol is localized mainly to deposits in the choriocapillaris and Bruch's membrane and on the surfaces of vascular endothelial cells of the neural retina. RPE/choriocapillaris regions contained approximately four times more 7kCh than the neural retina. In ARPE19 cells and HMVECs, oxidized LDL and 7kCh induced VEGF 8- to 10-fold above controls. Hypoxia inducible factor (HIF)-1α levels did not increase as a result of 7kCh treatment, suggesting an HIF-independent induction pathway. Cholesterol sulfate, a liver X receptor (LXR) antagonist, had marked attenuation of the 7kCh-mediated VEGF induction. LXR-specific siRNAs also reduced VEGF induction. Inhibition of NF-κB with BAY 11-7082 reduced IL-8 but not VEGF induction. CONCLUSIONS. The location of 7-kCh in the retina and its induction of VEGF in cultured RPE cells and HMVECs suggest it may play a critical role in choroidal neovascularization. The pathway for VEGF induction seems to be independent of HIF-1α and NF-κB but seems to be partially regulated by LXRs. Copyright © Association for Research in Vision and Ophthalmology
Integrins: Moonlighting Proteins in Invadosome Formation
No full textInvadopodia are actin-rich protrusions developed by transformed cells in 2D/3D environments that are implicated in extracellular matrix (ECM) remodeling and degradation. These structures have an undoubted association with cancer invasion and metastasis because invadopodium formation in vivo is a key step for intra/extravasation of tumor cells. Invadopodia are closely related to other actin-rich structures known as podosomes, which are typical structures of normal cells necessary for different physiological processes during development and organogenesis. Invadopodia and podosomes are included in the general term ‘invadosomes,’ as they both appear as actin puncta on plasma membranes next to extracellular matrix metalloproteinases, although organization, regulation, and function are slightly different. Integrins are transmembrane proteins implicated in cell–cell and cell–matrix interactions and other important processes such as molecular signaling, mechano-transduction, and cell functions, e.g., adhesion, migration, or invasion. It is noteworthy that integrin expression is altered in many tumors, and other pathologies such as cardiovascular or immune dysfunctions. Over the last few years, growing evidence has suggested a role of integrins in the formation of invadopodia. However, their implication in invadopodia formation and adhesion to the ECM is still not well known. This review focuses on the role of integrins in invadopodium formation and provides a general overview of the involvement of these proteins in the mechanisms of metastasis, taking into account classic research through to the latest and most advanced work in the field
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