Unusual astrocyte reactivity caused by the food mycotoxin ochratoxin A in aggregating rat brain cell cultures.

Zurich, M-G; Lengacher, S; Braissant, O; Monnet-Tschudi, F; Pellerin, L; Honegger, P

Zurich, M-G; Lengacher, S; Braissant, O; Monnet-Tschudi, F; Pellerin, L; Honegger, P.

Afiliación

Zurich MG; Department of Physiology, University of Lausanne, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland. mzurich@unil.ch

Neuroscience ; 134(3): 771-82, 2005.

Article en En | MEDLINE | ID: mdl-15994020

RESUMEN

Ochratoxin A (OTA), a mycotoxin and widespread food contaminant, is known for its patent nephrotoxicity and potential neurotoxicity. Previous observations in vitro showed that in the CNS, glial cells were particularly sensitive to OTA. In the search for the molecular mechanisms underlying OTA neurotoxicity, we investigated the relationship between OTA toxicity and glial reactivity, in serum-free aggregating brain cell cultures. Using quantitative reverse transcriptase-polymerase chain reaction to analyze changes in gene expression, we found that in astrocytes, non cytotoxic concentrations of OTA down-regulated glial fibrillary acidic protein, while it up-regulated vimentin and the peroxisome proliferator-activated receptor-gamma expression. OTA also up-regulated the inducible nitric oxide synthase and the heme oxygenase-1. These OTA-induced alterations in gene expression were more pronounced in cultures at an advanced stage of maturation. The natural peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-delta(12,14) prostaglandin J2, and the cyclic AMP analog, bromo cyclic AMP, significantly attenuated the strong induction of peroxisome proliferator-activated receptor-gamma and inducible nitric oxide synthase, while they partially reversed the inhibitory effect of OTA on glial fibrillary acidic protein. The present results show that OTA affects the cytoskeletal integrity of astrocytes as well as the expression of genes pertaining to the brain inflammatory response system, and suggest that a relationship exists between the inflammatory events and the cytoskeletal changes induced by OTA. Furthermore, these results suggest that, by inducing an atypical glial reactivity, OTA may severely affect the neuroprotective capacity of glial cells.

Asunto(s)

Astrocitos/efectos de los fármacos; Regulación de la Expresión Génica/efectos de los fármacos; Micotoxinas/farmacología; Ocratoxinas/farmacología; Animales; Astrocitos/fisiología; Encéfalo/citología; Agregación Celular/efectos de los fármacos; Células Cultivadas; Medio de Cultivo Libre de Suero/farmacología; AMP Cíclico/metabolismo; AMP Cíclico/farmacología; Relación Dosis-Respuesta a Droga; Interacciones Farmacológicas; Embrión de Mamíferos; Líquido Extracelular/efectos de los fármacos; Líquido Extracelular/metabolismo; Proteína Ácida Fibrilar de la Glía/genética; Proteína Ácida Fibrilar de la Glía/metabolismo; Glutamato-Amoníaco Ligasa/genética; Glutamato-Amoníaco Ligasa/metabolismo; Hemo Oxigenasa (Desciclizante)/genética; Hemo Oxigenasa (Desciclizante)/metabolismo; Hemo-Oxigenasa 1; Hidroliasas/metabolismo; Inmunohistoquímica/métodos; Hibridación in Situ/métodos; Óxido Nítrico Sintasa/genética; Óxido Nítrico Sintasa/metabolismo; Óxido Nítrico Sintasa de Tipo II; PPAR gamma/genética; PPAR gamma/metabolismo; Prostaglandina D2/análogos & derivados; Prostaglandina D2/farmacología; ARN Mensajero/metabolismo; Ratas; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos; Factores de Tiempo; Vimentina/genética; Vimentina/metabolismo

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Astrocitos / Micotoxinas / Ocratoxinas Idioma: En Revista: Neuroscience Año: 2005 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos

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