RESUMO
DJ-1 plays an important role in oxidative stress, and is involved in various neurodegenerative diseases. Accumulating evidence suggests a central role for oxidative stress in multiple sclerosis (MS). The aim of this study was to examine whether changes occur in DJ-1 expression in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). We found upregulation of DJ-1 mRNA and protein expression levels in EAE and a correlation between disease severity and increased DJ-1 levels. Although DJ-1 isoforms were more alkaline in controls, in EAE, a shift was noted toward acidic isoforms. ROS induced by SIN-I exposure led to an increase in DJ-1 mRNA and protein levels in human glioma U-87 cells. Immunocytochemical staining demonstrated that DJ-1 is present both in the cytoplasm and the nuclei of these cells. This is the first report of modulation of DJ-1 expression in EAE. Upregulation of DJ-1 was noted in EAE, and similar results were observed in glioma cells exposed to ROS. In view of the accumulating evidence on the central role of oxidative stress in MS, and the importance of DJ-1 in oxidative stress management by the CNS, we believe that DJ-1 will be found to have a central role in MS.
Assuntos
Encefalomielite Autoimune Experimental/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Esclerose Múltipla/metabolismo , Proteínas Oncogênicas/metabolismo , Estresse Oxidativo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos C3H , Morfolinas/química , Morfolinas/farmacologia , Proteínas Oncogênicas/genética , Peroxirredoxinas , Proteína Desglicase DJ-1 , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sidnonas/química , Sidnonas/farmacologia , Regulação para CimaRESUMO
Because of their unique attributes of plasticity and accessibility, bone marrow-derived mesenchymal stem cells (MSCs) may find use for therapy of neurodegenerative disorders. Our previous studies of adult human MSCs demonstrated that these cells express an extensive assortment of neural genes at a low but clearly detectable level. Here, we report expression of 12 neural genes, 8 genes related to the neuro-dopaminergic system, and 11 transcription factors with neural significance by human MSCs. Our results suggest that, as opposed to cells that do not express neural genes, human MSCs are predisposed to differentiate to neuronal and glial lineages, given the proper conditions. Our findings add a new dimension in which to view adult stem cell plasticity, and may explain the relative ease with which MSCs, transplanted into the central nervous system (CNS) differentiate to a variety of functional neural cell types. Our results further promote the possibility that adult human MSCs are promising candidates for cell-based therapy of neurodegenerative diseases.
Assuntos
Expressão Gênica/genética , Células-Tronco Mesenquimais/metabolismo , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/genética , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo , Adulto , Idoso , Animais , Antígenos CD/análise , Western Blotting , Células da Medula Óssea/química , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Separação Celular , Células Cultivadas , Citometria de Fluxo , Humanos , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Neurônios/química , Neurônios/citologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Erythropoietin (Epo) has been shown in the recent years to have neuroprotective activity in a variety of settings. In this study, we investigated its impact on the progression of paralysis in a mouse model simulating the human disorder amyotrophic lateral sclerosis (ALS). We found that Epo can delay the onset of motor deterioration in transgenic SOD G93A mice without prolonging their survival. Notably this effect was selective for the females only. These initial findings encourage further investigation of this biological avenue in the search for improved remedies for this fatal disease.