Nora Rotstein - Academia.edu (original) (raw)

Papers by Nora Rotstein

Research paper thumbnail of Sphingolipid Signaling in Mammalian Photoreceptor Cells

Investigative Ophthalmology & Visual Science, Mar 26, 2012

Research paper thumbnail of Pigment epithelium-derived factor (PEDF) prevents apoptosis and promotes apical localization of opsin in retina photoreceptors

Background: PEDF has neurotrophic activity and interacts with PEDF-R, a membrane-linked lipase. R... more Background: PEDF has neurotrophic activity and interacts with PEDF-R, a membrane-linked lipase. Results: A PEDF-binding region of PEDF-R is required for PEDF-R enzymatic stimulation, and peptides derived from this region block PEDF⅐PEDF-R-mediated retinal survival activities. Conclusion: A ligand binding domain is identified in PEDF-R, a critical receptor for the survival activity of PEDF. Significance: The findings provide mechanistic insight into the survival activity of PEDF. The extracellular pigment epithelium-derived factor (PEDF) displays retina survival activity by interacting with receptor proteins on cell surfaces. We have previously reported that PEDF binds and stimulates PEDF receptor (PEDF-R), a transmembrane phospholipase. However, the PEDF binding site of PEDF-R and its involvement in survival activity have not been identified. The purpose of this work is to identify a biologically relevant ligand

Research paper thumbnail of Sphingosine-1-Phosphate: A Key Mediator in the Survival and Development of Retina Photoreceptors

Investigative Ophthalmology & Visual Science, Apr 28, 2009

Research paper thumbnail of Sphingosine-1-phosphate and ceramide-1-phosphate promote migration, pro-inflammatory and pro-fibrotic responses in retinal pigment epithelium cells

Experimental Eye Research

Research paper thumbnail of Lif Protects Photoreceptors From Induced Oxidative Stress in Pure Primary Neuronal Cultures of Retina

Investigative Ophthalmology & Visual Science, 2008

Research paper thumbnail of Sphingosine-1-Phosphate Has a Key Role in the Crosstalk and Development of Retina Glial and Neuronal Cells

Investigative Ophthalmology & Visual Science, 2010

Research paper thumbnail of Interactions With Müller Glial Cells Induce And Preserve Stem Cell Characteristics In Retinal Progenitors After Several Passages

Investigative Ophthalmology & Visual Science, 2011

Research paper thumbnail of Peptides derived from Pigmented Epithelium-derived Factor (PEDF) prevent apoptosis and promote apical localization of rhodopsin in retinal photoreceptors

Investigative Ophthalmology & Visual Science, 2020

Research paper thumbnail of Proliferation of Retina Neuroblasts in Cocultures of Muller Cells and Retinal Neurons: Effects of Docosahexaenoic Acid on Photoreceptor Differentiation

Investigative Ophthalmology & Visual Science, 2009

Research paper thumbnail of Trophic Factors Can Regulate Cell Cycle Progression, Differentiation and pax–6 Expression in Müller Cells

Investigative Ophthalmology & Visual Science, 2005

Research paper thumbnail of Ceramide Is a Key Mediator in the Apoptosis of Retina Photoreceptors

Investigative Ophthalmology & Visual Science, 2005

Research paper thumbnail of Estructura y funciones de la membrana

Según las evidencias actuales, la vida parece haber surgido hace más de 4.000 millones de años a ... more Según las evidencias actuales, la vida parece haber surgido hace más de 4.000 millones de años a partir de moléculas sencillas denominadas ácidos nucleicos. A diferencia de otros compuestos de esa época primitiva, los ácidos nucleicos, entre éstos el ácido desoxirribonucleico (ADN), adquirieron la capacidad de autorreplicarse, capacidad que les ha permitido perpetuarse en el tiempo.Fil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Research paper thumbnail of Retinoid X receptor activation promotes photoreceptor survival and modulates the inflammatory response in a mouse model of retinitis pigmentosa

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2021

Photoreceptor cell (PHR) death is a hallmark of most retinal neurodegenerative diseases, in which... more Photoreceptor cell (PHR) death is a hallmark of most retinal neurodegenerative diseases, in which inflammation plays a critical role. Activation of retinoid X receptors (RXR) modulates and integrates multiple cell functions, and has beneficial effects in animal models of chronic inflammatory diseases. Nonetheless, the mechanisms involved and their role in retina neuroprotection are poorly understood. In this work we assessed whether RXR activation prevents inflammation and/or PHR death in retinitis pigmentosa, an inherited retina neurodegeneration, using as an ex vivo model, retinas from the rd1 mice, a murine model of this disease. We demonstrated that rd1 retinas had lower levels of RXR alpha isoform than their wt counterparts at early developmental times, whereas its distribution pattern remained similar. In mixed neuro-glial cultures obtained from either rd1 or wt retinas, both PHR and Müller glial cells (MGC) expressed RXRalpha, and RXR activation by its synthetic pan-agonist PA024 selectively increased mRNA levels of RXRgamma isoform. PA024 decreased PHR death in rd1 mixed cultures; it reduced the amount of non-viable neurons, delayed the onset of PHR apoptosis, and decreased Bax mRNA levels. PA024 also reduced MGC reactivity in vitro before and at the onset of degeneration, decreasing GFAP expression, increasing glutamine synthetase mRNA levels, and promoting the transcription of the anti-inflammatory cytokine, Il-10. These results suggest that RXR activation rescues rd1 PHR and decreases MGC reactivity, promoting an anti-inflammatory environment in the rd1 retina, thus supporting the potential of RXR agonists as pharmacological tools for treating retina degenerative diseases.

Research paper thumbnail of Eicosapentaenoic Acid Is Metabolized To Docosahexaenoic Acid In Retina Neurons To Protect Photoreceptors From Apoptosis Induced By Oxidative Stress

Investigative Ophthalmology & Visual Science, 2012

Research paper thumbnail of Tipos de muerte celular

Fil: German, Olga Lorena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cien... more Fil: German, Olga Lorena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Bahia Blanca. Instituto de Investigaciones Bioquimicas de Bahia Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquimicas de Bahia Blanca; Argentina

Research paper thumbnail of The enrichment in docosahexaenoic acid (DHA) of mem- brane lipids in the nervous system has stimulated the search for the possible functions of this fatty acid in brain and reti

We have recently shown that docosahexaenoic acid (DHA) is necessary for survival and differentiat... more We have recently shown that docosahexaenoic acid (DHA) is necessary for survival and differentiation of rat retinal photoreceptors during development in vitro. In cultures lacking DHA, retinal neurons developed normally for 4 d; then photoreceptors selectively started an apoptotic pathway leading to extensive degeneration of these cells by day 11. DHA protected photoreceptors by delaying the onset of apoptosis; in addition, it advanced photoreceptor differentiation, promoting opsin expression and inducing apical differentiation in these neurons. DHA was the only fatty acid having these effects. Mitochondrial damage accompanied photoreceptor apoptosis and was markedly reduced upon DHA supplementation. This suggests that a possible mechanism of DHA-mediated photoreceptor protection might be the preservation of mitochondrial activity; a critical amount of DHA in mitochondrial phospholipids might be required for proper functioning of these organelles, which in turn might be essential to...

Research paper thumbnail of Differentiation of Neuroblasts Into Photoreceptors in Co-Cultures of Muller Glial Cells and Neurons: Regulation of Apoptosis by Docosahexaenoic Acid and Sphingosine-1-Phosphate

Investigative Ophthalmology & Visual Science, 2010

Research paper thumbnail of Muller Glial Cells Promote The Differentiation Of Retinal Progenitors As Photoreceptors And Sphingosine-1-Phosphate And Docosahexaenoic Acid Prevent Their Apoptosis

Research paper thumbnail of Activation Of The p38 MAP/kinase Pathway Is Required For Retinoic Acid Effects On Retina Photoreceptors

Investigative Ophthalmology & Visual Science, 2012

Research paper thumbnail of Pigmented Epithelial Cells ARPE-19 and Docosahexaenoic Acid Promote Cell Differentiation and Spatial Organization of Retina Photoreceptors in vitro

Investigative Ophthalmology & Visual Science, 2007

Research paper thumbnail of Sphingolipid Signaling in Mammalian Photoreceptor Cells

Investigative Ophthalmology & Visual Science, Mar 26, 2012

Research paper thumbnail of Pigment epithelium-derived factor (PEDF) prevents apoptosis and promotes apical localization of opsin in retina photoreceptors

Background: PEDF has neurotrophic activity and interacts with PEDF-R, a membrane-linked lipase. R... more Background: PEDF has neurotrophic activity and interacts with PEDF-R, a membrane-linked lipase. Results: A PEDF-binding region of PEDF-R is required for PEDF-R enzymatic stimulation, and peptides derived from this region block PEDF⅐PEDF-R-mediated retinal survival activities. Conclusion: A ligand binding domain is identified in PEDF-R, a critical receptor for the survival activity of PEDF. Significance: The findings provide mechanistic insight into the survival activity of PEDF. The extracellular pigment epithelium-derived factor (PEDF) displays retina survival activity by interacting with receptor proteins on cell surfaces. We have previously reported that PEDF binds and stimulates PEDF receptor (PEDF-R), a transmembrane phospholipase. However, the PEDF binding site of PEDF-R and its involvement in survival activity have not been identified. The purpose of this work is to identify a biologically relevant ligand

Research paper thumbnail of Sphingosine-1-Phosphate: A Key Mediator in the Survival and Development of Retina Photoreceptors

Investigative Ophthalmology & Visual Science, Apr 28, 2009

Research paper thumbnail of Sphingosine-1-phosphate and ceramide-1-phosphate promote migration, pro-inflammatory and pro-fibrotic responses in retinal pigment epithelium cells

Experimental Eye Research

Research paper thumbnail of Lif Protects Photoreceptors From Induced Oxidative Stress in Pure Primary Neuronal Cultures of Retina

Investigative Ophthalmology & Visual Science, 2008

Research paper thumbnail of Sphingosine-1-Phosphate Has a Key Role in the Crosstalk and Development of Retina Glial and Neuronal Cells

Investigative Ophthalmology & Visual Science, 2010

Research paper thumbnail of Interactions With Müller Glial Cells Induce And Preserve Stem Cell Characteristics In Retinal Progenitors After Several Passages

Investigative Ophthalmology & Visual Science, 2011

Research paper thumbnail of Peptides derived from Pigmented Epithelium-derived Factor (PEDF) prevent apoptosis and promote apical localization of rhodopsin in retinal photoreceptors

Investigative Ophthalmology & Visual Science, 2020

Research paper thumbnail of Proliferation of Retina Neuroblasts in Cocultures of Muller Cells and Retinal Neurons: Effects of Docosahexaenoic Acid on Photoreceptor Differentiation

Investigative Ophthalmology & Visual Science, 2009

Research paper thumbnail of Trophic Factors Can Regulate Cell Cycle Progression, Differentiation and pax–6 Expression in Müller Cells

Investigative Ophthalmology & Visual Science, 2005

Research paper thumbnail of Ceramide Is a Key Mediator in the Apoptosis of Retina Photoreceptors

Investigative Ophthalmology & Visual Science, 2005

Research paper thumbnail of Estructura y funciones de la membrana

Según las evidencias actuales, la vida parece haber surgido hace más de 4.000 millones de años a ... more Según las evidencias actuales, la vida parece haber surgido hace más de 4.000 millones de años a partir de moléculas sencillas denominadas ácidos nucleicos. A diferencia de otros compuestos de esa época primitiva, los ácidos nucleicos, entre éstos el ácido desoxirribonucleico (ADN), adquirieron la capacidad de autorreplicarse, capacidad que les ha permitido perpetuarse en el tiempo.Fil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Research paper thumbnail of Retinoid X receptor activation promotes photoreceptor survival and modulates the inflammatory response in a mouse model of retinitis pigmentosa

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2021

Photoreceptor cell (PHR) death is a hallmark of most retinal neurodegenerative diseases, in which... more Photoreceptor cell (PHR) death is a hallmark of most retinal neurodegenerative diseases, in which inflammation plays a critical role. Activation of retinoid X receptors (RXR) modulates and integrates multiple cell functions, and has beneficial effects in animal models of chronic inflammatory diseases. Nonetheless, the mechanisms involved and their role in retina neuroprotection are poorly understood. In this work we assessed whether RXR activation prevents inflammation and/or PHR death in retinitis pigmentosa, an inherited retina neurodegeneration, using as an ex vivo model, retinas from the rd1 mice, a murine model of this disease. We demonstrated that rd1 retinas had lower levels of RXR alpha isoform than their wt counterparts at early developmental times, whereas its distribution pattern remained similar. In mixed neuro-glial cultures obtained from either rd1 or wt retinas, both PHR and Müller glial cells (MGC) expressed RXRalpha, and RXR activation by its synthetic pan-agonist PA024 selectively increased mRNA levels of RXRgamma isoform. PA024 decreased PHR death in rd1 mixed cultures; it reduced the amount of non-viable neurons, delayed the onset of PHR apoptosis, and decreased Bax mRNA levels. PA024 also reduced MGC reactivity in vitro before and at the onset of degeneration, decreasing GFAP expression, increasing glutamine synthetase mRNA levels, and promoting the transcription of the anti-inflammatory cytokine, Il-10. These results suggest that RXR activation rescues rd1 PHR and decreases MGC reactivity, promoting an anti-inflammatory environment in the rd1 retina, thus supporting the potential of RXR agonists as pharmacological tools for treating retina degenerative diseases.

Research paper thumbnail of Eicosapentaenoic Acid Is Metabolized To Docosahexaenoic Acid In Retina Neurons To Protect Photoreceptors From Apoptosis Induced By Oxidative Stress

Investigative Ophthalmology & Visual Science, 2012

Research paper thumbnail of Tipos de muerte celular

Fil: German, Olga Lorena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cien... more Fil: German, Olga Lorena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Bahia Blanca. Instituto de Investigaciones Bioquimicas de Bahia Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquimicas de Bahia Blanca; Argentina

Research paper thumbnail of The enrichment in docosahexaenoic acid (DHA) of mem- brane lipids in the nervous system has stimulated the search for the possible functions of this fatty acid in brain and reti

We have recently shown that docosahexaenoic acid (DHA) is necessary for survival and differentiat... more We have recently shown that docosahexaenoic acid (DHA) is necessary for survival and differentiation of rat retinal photoreceptors during development in vitro. In cultures lacking DHA, retinal neurons developed normally for 4 d; then photoreceptors selectively started an apoptotic pathway leading to extensive degeneration of these cells by day 11. DHA protected photoreceptors by delaying the onset of apoptosis; in addition, it advanced photoreceptor differentiation, promoting opsin expression and inducing apical differentiation in these neurons. DHA was the only fatty acid having these effects. Mitochondrial damage accompanied photoreceptor apoptosis and was markedly reduced upon DHA supplementation. This suggests that a possible mechanism of DHA-mediated photoreceptor protection might be the preservation of mitochondrial activity; a critical amount of DHA in mitochondrial phospholipids might be required for proper functioning of these organelles, which in turn might be essential to...

Research paper thumbnail of Differentiation of Neuroblasts Into Photoreceptors in Co-Cultures of Muller Glial Cells and Neurons: Regulation of Apoptosis by Docosahexaenoic Acid and Sphingosine-1-Phosphate

Investigative Ophthalmology & Visual Science, 2010

Research paper thumbnail of Muller Glial Cells Promote The Differentiation Of Retinal Progenitors As Photoreceptors And Sphingosine-1-Phosphate And Docosahexaenoic Acid Prevent Their Apoptosis

Research paper thumbnail of Activation Of The p38 MAP/kinase Pathway Is Required For Retinoic Acid Effects On Retina Photoreceptors

Investigative Ophthalmology & Visual Science, 2012

Research paper thumbnail of Pigmented Epithelial Cells ARPE-19 and Docosahexaenoic Acid Promote Cell Differentiation and Spatial Organization of Retina Photoreceptors in vitro

Investigative Ophthalmology & Visual Science, 2007