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1.
Biochim Biophys Acta Mol Cell Res ; 1868(11): 119098, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34271041

RESUMO

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.


Assuntos
Modelos Animais de Doenças , Inflamação/metabolismo , Células Fotorreceptoras/metabolismo , Retinose Pigmentar/metabolismo , Receptores X de Retinoides/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
2.
Nat Commun ; 12(1): 3328, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099654

RESUMO

Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of Drosophila larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Ecdisona/farmacologia , Epiderme/metabolismo , Morfogênese/efeitos dos fármacos , Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Drosophila/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Ecdisona/genética , Células Epidérmicas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Larva/metabolismo , Metamorfose Biológica , Morfogênese/genética , Receptores Acoplados a Proteínas G/genética , Relaxina/metabolismo
3.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1865(10): 158767, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32736090

RESUMO

The presence, biosynthesis and functional role of sterols in the green microalga Haematococcus pluvialis remain poorly understood. In this work we studied the effect of high-light (HL) stress on sterol synthesis in H. pluvialis UTEX 2505 cells. HL stress induced the synthesis of sterols in parallel with that of triacylglycerides (TAG), giving rise to the synthesis of cholesterol over that of phytosterols. Blockage of the carotenogenic 1-deoxy-D-xylulose 5-phosphate (MEP) pathway is shown to be involved in HL-induced sterol synthesis. In addition, high irradiance exposure induced MEP- and fatty acid (FA)-biosynthetic transcripts. The pharmacological inhibition of these pathways suggests a possible feedback regulation of sterol and FA homeostasis. Finally, both lipid classes proved crucial to the adequate photosynthetic performance of H. pluvialis grown under HL intensity stress. Our findings reveal new insights into H. pluvialis lipid metabolism that contribute to the development of value-added bioproducts from microalgae.


Assuntos
Metabolismo dos Lipídeos/efeitos da radiação , Lipídeos/genética , Fotossíntese/genética , Esteróis/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Luz , Metabolismo dos Lipídeos/genética , Microalgas/genética , Microalgas/metabolismo , Microalgas/efeitos da radiação , Fotossíntese/efeitos da radiação , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos da radiação , Xantofilas/metabolismo , Xantofilas/efeitos da radiação
4.
Front Cell Neurosci ; 13: 334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402853

RESUMO

Müller glial cells (MGC) are stem cells in the retina. Although their regenerative capacity is very low in mammals, the use of MGC as stem cells to regenerate photoreceptors (PHRs) during retina degenerations, such as in retinitis pigmentosa, is being intensely studied. Changes affecting PHRs in diseased retinas have been thoroughly investigated; however, whether MGC are also affected is still unclear. We here investigated whether MGC in retinal degeneration 1 (rd1) mouse, an animal model of retinitis pigmentosa, have impaired stem cell properties or structure. rd1 MGC showed an altered morphology, both in culture and in the whole retina. Using mixed neuron-glial cultures obtained from newborn mice retinas, we determined that proliferation was significantly lower in rd1 than in wild type (wt) MGC. Levels of stem cell markers, such as Nestin and Sox2, were also markedly reduced in rd1 MGC compared to wt MGC in neuron-glial cultures and in retina cryosections, even before the onset of PHR degeneration. We then investigated whether neuron-glial crosstalk was involved in these changes. Noteworthy, Nestin expression was restored in rd1 MGC in co-culture with wt neurons. Conversely, Nestin expression decreased in wt MGC in co-culture with rd1 neurons, as occurred in rd1 MGC in rd1 neuron-glial mixed cultures. These results imply that MGC proliferation and stem cell markers are reduced in rd1 retinas and might be restored by their interaction with "healthy" PHRs, suggesting that alterations in rd1 PHRs lead to a disruption in neuron-glial crosstalk affecting the regenerative potential of MGC.

5.
PLoS Negl Trop Dis ; 12(12): e0007021, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30557347

RESUMO

Nematode parasites cause substantial morbidity to billions of people and considerable losses in livestock and food crops. The repertoire of effective anthelmintic compounds for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance has become a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system, we here screened the nematicidal potential of novel imidazolium and imidazole derivatives. One of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. This lethal effect appears to be specific because DII concentrations which prove to be toxic to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster, and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 has been largely reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously unidentified UNC-29-containing muscle AChR, different from the classical L-AChR. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. Its lethality on C. elegans, its harmlessness in non-nematode species and its novel and dual mechanism of action make DII a promising candidate compound for anthelmintic therapy.


Assuntos
Anti-Helmínticos/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Imidazóis/farmacologia , Animais , Anti-Helmínticos/síntese química , Anti-Helmínticos/química , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Feminino , Células HEK293 , Humanos , Imidazóis/síntese química , Imidazóis/química , Masculino , Estrutura Molecular , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo
6.
Mech Dev ; 154: 44-50, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29715504

RESUMO

Many insects, like cockroaches, moths, and flies, can regenerate tissues by extending the growth-competent phases of their life cycle. The molecular and cellular players mediating this coordination between tissue growth and developmental timing have been recently discovered in Drosophila. The insulin/relaxin-like peptide, Dilp8, was identified as a factor communicating abnormal growth status of Drosophila larval imaginal discs to the neuroendocrine centers that control the timing of the onset of metamorphosis. Dilp8 requires a neuronal relaxin receptor for this function, the Leucine rich repeat containing G protein coupled receptor, Lgr3. A review of current data supports a model where imaginal disc-derived Dilp8 acts on four central nervous system Lgr3-positive neurons to activate cyclic-AMP signaling in an Lgr3-dependent manner. This causes a reduction in ecdysone hormone production by the larval endocrine prothoracic gland, which leads to a delay in the onset of metamorphosis and a simultaneous slowing down in the growth rates of healthy imaginal tissues, promoting the generation of proportionate individuals. We discuss reports indicating that the Dilp8-Lgr3 pathway might have other functions at different life history stages, which remain to be elucidated, and review molecular evolution data on invertebrate genes related to the relaxin-pathway. The strong conservation of the relaxin pathway throughout animal evolution contrasts with instances of its complete loss in some clades, such as lepidopterans, which must coordinate growth and developmental timing using another mechanism. Research into these areas should generate exciting new insights into the biology of growth coordination, the evolution of the relaxin signaling pathway, and likely reveal unforeseen functions in other developmental stages.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Relaxina/metabolismo , Transdução de Sinais/fisiologia , Animais , Humanos , Neurônios/metabolismo , Receptores de Peptídeos/metabolismo
7.
J Neurochem ; 136(5): 931-46, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26662863

RESUMO

Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here, we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat and hydrogen peroxide (H2 O2 ). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in retina photoreceptors, and its precursor, eicosapentaenoic acid (EPA) have multiple beneficial effects. Here, we show that retina neurons in vitro express the desaturase FADS2 and can synthesize DHA from EPA. Moreover, addition of EPA to these cultures protects photoreceptors from oxidative stress and promotes their differentiation through its metabolization to DHA.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células Fotorreceptoras de Vertebrados/metabolismo , Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Mitocôndrias/metabolismo , Paraquat/farmacologia , Substâncias Protetoras/farmacologia , Ratos Wistar , Retina/metabolismo
8.
Nat Commun ; 6: 8732, 2015 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-26510564

RESUMO

How different organs in the body sense growth perturbations in distant tissues to coordinate their size during development is poorly understood. Here we mutate an invertebrate orphan relaxin receptor gene, the Drosophila Leucine-rich repeat-containing G protein-coupled receptor 3 (Lgr3), and find body asymmetries similar to those found in insulin-like peptide 8 (dilp8) mutants, which fail to coordinate growth with developmental timing. Indeed, mutation or RNA intereference (RNAi) against Lgr3 suppresses the delay in pupariation induced by imaginal disc growth perturbation or ectopic Dilp8 expression. By tagging endogenous Lgr3 and performing cell type-specific RNAi, we map this Lgr3 activity to a new subset of CNS neurons, four of which are a pair of bilateral pars intercerebralis Lgr3-positive (PIL) neurons that respond specifically to ectopic Dilp8 by increasing cAMP-dependent signalling. Our work sheds new light on the function and evolution of relaxin receptors and reveals a novel neuroendocrine circuit responsive to growth aberrations.


Assuntos
Encéfalo/crescimento & desenvolvimento , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Encéfalo/metabolismo , AMP Cíclico/metabolismo , Drosophila/genética , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Discos Imaginais/crescimento & desenvolvimento , Discos Imaginais/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Dados de Sequência Molecular , Receptores Acoplados a Proteínas G/genética , Relaxina/metabolismo , Transdução de Sinais
9.
Science ; 336(6081): 579-82, 2012 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-22556250

RESUMO

Developing animals frequently adjust their growth programs and/or their maturation or metamorphosis to compensate for growth disturbances (such as injury or tumor) and ensure normal adult size. Such plasticity entails tissue and organ communication to preserve their proportions and symmetry. Here, we show that imaginal discs autonomously activate DILP8, a Drosophila insulin-like peptide, to communicate abnormal growth and postpone maturation. DILP8 delays metamorphosis by inhibiting ecdysone biosynthesis, slowing growth in the imaginal discs, and generating normal-sized animals. Loss of dilp8 yields asymmetric individuals with an unusually large variation in size and a more varied time of maturation. Thus, DILP8 is a fundamental element of the hitherto ill-defined machinery governing the plasticity that ensures developmental stability and robustness.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Discos Imaginais/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Metamorfose Biológica , Sequência de Aminoácidos , Animais , Apoptose , Proteínas de Drosophila/química , Drosophila melanogaster/metabolismo , Ecdisona/biossíntese , Metanossulfonato de Etila/farmacologia , Regulação da Expressão Gênica no Desenvolvimento , Genes de Insetos , Discos Imaginais/crescimento & desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Larva/crescimento & desenvolvimento , Metamorfose Biológica/genética , Dados de Sequência Molecular , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Pupa/crescimento & desenvolvimento , Regeneração
10.
J Neurosci Res ; 86(7): 1459-71, 2008 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18189319

RESUMO

The finding that Müller cells have stem cell properties in the retina has led to the hypothesis that they might be a source for replacing neurons lost in neurodegenerative diseases. However, utilization of Müller cells for regenerative purposes in the mammalian eye still requires identifying those factors that regulate their multipotentiality and proliferation. In addition, because Pax6 expression is indispensable for eye development, its regulation would be required during regeneration. In the present study we investigated the regulation of cell-cycle progression and Pax6 expression in pure Müller glial cell cultures and neuroglial cocultures from rat retinas. At early times in vitro, glial cells showed high expression of Pax6 and of nestin, a stem cell marker, and of markers of cell-cycle progression; expression of these markers decreased during development in parallel with increased glial differentiation. The addition of glial-derived neurotrophic factor, basic fibroblast growth factor, and insulin restored proliferation and also Pax6 and nestin expression in glial cells. Noteworthy, in neuroglial cocultures Müller cells retained Pax6 expression for longer periods, and, in turn, neuronal progenitors preserved their proliferative potential for several days in vitro. This suggests that neuroglial interactions mutually regulate their mitogenic capacity. In addition, in glial secondary cultures incubated with insulin, many neuroblast-like cells expressed the neuronal marker NeuN. Our results suggest that the proliferative capacity and the features of eye stem cells of Müller glial cells are regulated by molecular and cellular factors, which might then provide potential tools for manipulating retinal regeneration.


Assuntos
Ciclo Celular/fisiologia , Proteínas do Olho/metabolismo , Expressão Gênica/fisiologia , Proteínas de Homeodomínio/metabolismo , Fatores de Crescimento Neural/metabolismo , Neuroglia/metabolismo , Neurônios/fisiologia , Fatores de Transcrição Box Pareados/metabolismo , Proteínas Repressoras/metabolismo , Células-Tronco/fisiologia , Albinismo , Animais , Animais Recém-Nascidos , Bromodesoxiuridina , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Células Cultivadas , Técnicas de Cocultura/métodos , Proteínas do Olho/genética , Expressão Gênica/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Marcação In Situ das Extremidades Cortadas/métodos , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Ratos , Proteínas Repressoras/genética , Retina/citologia , Fatores de Tempo
11.
Invest Ophthalmol Vis Sci ; 47(7): 3017-27, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16799048

RESUMO

PURPOSE: The precise molecular cues required for photoreceptor development are still unknown. Pax6 and Crx are essential during early retinal development and for photoreceptor differentiation, respectively. The lipid molecule docosahexaenoic acid (DHA) has also been shown to promote photoreceptor differentiation. Pax6 expression during the early steps in photoreceptor development and whether the mutual contribution of Crx and DHA enhances photoreceptor differentiation were investigated. METHODS: Neuroblast proliferation, Crx, and Pax6 expression were investigated in rat retinas in vivo and in neuronal cultures with or without DHA. BrdU incorporation, nestin and opsin expression, apical differentiation, and axonal outgrowth were determined by phase microscopy and immunochemistry. RESULTS: Pax6 expression occurred in all proliferating retinal neuroblasts in vivo; however, after their last mitotic division, photoreceptors stopped expressing Pax6 and started expressing Crx. In vitro, photoreceptor progenitors also showed a switch from Pax6 to Crx expression immediately after they exited the cell cycle and started differentiation. In contrast, those progenitors differentiating into amacrine neurons continued expressing Pax6 and did not express Crx. Most postmitotic photoreceptors expressing Crx showed little axon development and few of them expressed opsin. The addition of DHA dramatically increased differentiation in Crx-positive photoreceptors, enhancing opsin expression, apical differentiation, and axonal outgrowth, without affecting Crx expression. CONCLUSIONS: The results suggest that Pax6 and Crx expression are mutually exclusive during photoreceptor differentiation. Onset of Crx expression may provide a permissive stage that is essential to initiate photoreceptor differentiation, but additional support of DHA, among other environmental signals, is necessary to accomplish further differentiation.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Proteínas de Homeodomínio/metabolismo , Células Fotorreceptoras de Vertebrados/citologia , Retina/embriologia , Transativadores/metabolismo , Animais , Axônios/fisiologia , Bromodesoxiuridina/metabolismo , Técnicas de Cultura de Células , Proteínas do Olho/metabolismo , Feminino , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/metabolismo , Microscopia de Contraste de Fase , Proteínas do Tecido Nervoso/metabolismo , Nestina , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Gravidez , Ratos , Ratos Wistar , Proteínas Repressoras/metabolismo , Retina/metabolismo , Opsinas de Bastonetes/metabolismo
12.
J Neuroimmunol ; 160(1-2): 154-61, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15710468

RESUMO

The presence of nicotinic receptors (nAChRs) in blood cells has been demonstrated. However, little is known about their functional roles. We have detected mRNA of alpha7 nAChR in peripheral human lymphocytes and determined that its expression is highly variable among individuals and within the same individual at different times. Upregulation of alpha7 is systematically observed after incubation of lymphocytes with nicotine or alpha-bungarotoxin. In addition, the incubation with these drugs decreases the percentage of apoptotic cells induced by the exposure to cortisol. Our results suggest that alpha7 nAChRs are involved in the modulation of cortisol-induced apoptosis.


Assuntos
Apoptose/imunologia , Linfócitos/citologia , Linfócitos/metabolismo , Receptores Nicotínicos/fisiologia , Adulto , Animais , Apoptose/efeitos dos fármacos , Bungarotoxinas/farmacologia , Células Cultivadas , Humanos , Hidrocortisona/farmacologia , Linfócitos/efeitos dos fármacos , Músculo Esquelético/metabolismo , Nicotina/farmacologia , Antagonistas Nicotínicos/farmacologia , Oxirredução , Subunidades Proteicas/biossíntese , Subunidades Proteicas/genética , RNA Mensageiro/análise , Ratos , Ratos Wistar , Receptores Nicotínicos/biossíntese , Receptores Nicotínicos/genética , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo , Regulação para Cima/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7
13.
Invest Ophthalmol Vis Sci ; 44(5): 2235-44, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12714666

RESUMO

PURPOSE: A recent study has shown that glia-derived neurotrophic factor (GDNF) and docosahexaenoic acid (DHA) promote the survival and differentiation of retina photoreceptors. The current study was undertaken to investigate whether these molecules participate in cell cycle regulation in retinal progenitors in vitro. METHODS: Developmental changes in the expression of the stem cell marker nestin and of cell cycle and differentiated neuron markers were analyzed in neuroblasts obtained from 1-day-old rat retinas. The effects of GDNF and DHA on those changes were then determined. RESULTS: Expression of nestin, found in more than one third of neuroblasts at day 1, rapidly decreased during development, with most neuroblasts acquiring the photoreceptor phenotype. GDNF increased the percentage of photoreceptor progenitors expressing nestin, whereas DHA reduced it, simultaneously enhancing photoreceptor differentiation. Several markers of cell cycle progression indicated that photoreceptor progenitors maintained an active cell cycle during the first 2 days in vitro. GDNF stimulated the cell cycle, increasing the number of dividing cells and generating more photoreceptor progenitors, whereas DHA induced cell cycle exit and photoreceptor differentiation. Analysis of the expression of the cyclin-Cdk inhibitor p27(Kip1) confirmed these results. CONCLUSIONS: GDNF and DHA acted as molecular cues, counterbalancing the decision of photoreceptors to remain in or exit the cell cycle. The results strongly suggest that both factors participate in determining the number of photoreceptors in vitro, regulating the cell cycle and survival at early and late stages of development, respectively. Hence, GDNF and DHA may coordinately control the histogenesis of photoreceptors in the retina by modulating both neurogenesis and apoptosis.


Assuntos
Ciclo Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Fatores de Crescimento Neural/farmacologia , Proteínas do Tecido Nervoso , Retina/citologia , Células-Tronco/citologia , Animais , Animais Recém-Nascidos , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p27 , Regulação para Baixo , Técnica Indireta de Fluorescência para Anticorpo , Corantes Fluorescentes/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Indóis/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Nestina , Neurônios/citologia , Neurônios/metabolismo , Ratos , Ratos Wistar , Retina/metabolismo , Opsinas de Bastonetes/metabolismo , Células-Tronco/metabolismo , Proteínas Supressoras de Tumor/metabolismo
14.
Artigo em Espanhol | MEDLINE | ID: mdl-12934250

RESUMO

This anatomical study has been done to determine the different segments of the hypogastric artery with it's relationships and the place in which it should be surgically ligated in emergency situations, particularly gynecologic and obstetric.


Assuntos
Artéria Ilíaca/anatomia & histologia , Artéria Ilíaca/cirurgia , Humanos , Ligadura
15.
Rev. Fac. Cienc. Méd. (Córdoba) ; 59(1): 97-100, 2002. ilus
Artigo em Espanhol | LILACS | ID: lil-349524

RESUMO

Este estudio anatómico ha sido realizado para determinar los diversos segmentos que tiene la arteria hipog'strica sus relaciónes y el lugar en que quirúrgicamente debe realizarse su ligadura en situaciones de emergencia, particularmente ginecológicas y obstétricas


Assuntos
Humanos , Artéria Ilíaca , Complicações Intraoperatórias , Ligadura
16.
Artigo em Espanhol | BINACIS | ID: bin-39034

RESUMO

This anatomical study has been done to determine the different segments of the hypogastric artery with its relationships and the place in which it should be surgically ligated in emergency situations, particularly gynecologic and obstetric.

17.
Rev. Fac. Cienc. Méd. [Córdoba] ; 59(1): 97-100, 2002. ilus
Artigo em Espanhol | BINACIS | ID: bin-5332

RESUMO

Este estudio anatómico ha sido realizado para determinar los diversos segmentos que tiene la arteria hipogstrica sus relaciónes y el lugar en que quirúrgicamente debe realizarse su ligadura en situaciones de emergencia, particularmente ginecológicas y obstétricas (AU)


Assuntos
Humanos , Artéria Ilíaca/anatomia & histologia , Artéria Ilíaca/cirurgia , Complicações Intraoperatórias/cirurgia , Ligadura
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