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Angiogénesis anormal y respuestas a la privación de glucosa y oxígeno en ratones que carecen de la proteína ARNT
E Maltepe1, J V Schmidt, D Baunoch
1Department of Pathology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA.
Nature
|March 27, 1997
Resumen
El translocator nuclear del receptor de arilohidrocarburos (ARNT) es esencial para el desarrollo embrionario, ya que regula las respuestas al bajo nivel de oxígeno y glucosa. La deficiencia de ARNT en ratones conduce a la insuficiencia del desarrollo y la formación de vasos sanguíneos defectuosos.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
- Fisiología celular Fisiología celular.
Sus antecedentes:
- ARNT es un factor de transcripción en la familia bHLH-PAS, formando heterodímeros con AHR y HIF-1alpha.
- ARNT-AHR regula el metabolismo xenobiótico, mientras que ARNT-HIF-1alpha está involucrado en las respuestas de privación de oxígeno.
Objetivo del estudio:
- Investigar el papel del ARNT en el desarrollo embrionario y las respuestas celulares.
- Para aclarar la función de la ARNT en las vías de señalización de la hipoxia y la hipoglucemia.
Principales métodos:
- Disrupción dirigida del locus de Arnt en las células madre embrionarias de ratón.
- Análisis de la activación génica en las células Arnt-/-ES en condiciones hipóxicas e hipoglucémicas.
- Análisis fenotípico de los embriones Arnt-/.
Principales resultados:
- Las células Arnt-/-ES no pudieron activar los genes en respuesta a la baja tensión de oxígeno y la disminución de la glucosa.
- Arnt-/- embriones exhibieron letalidad embrionaria el día pasado 10.5.
- Se observó una angiogénesis defectuosa del saco vitelino y del arco branquial, retraso en el desarrollo y pérdida de embriones en embriones Arnt-/-.
Conclusiones:
- ARNT es crucial para la viabilidad embrionaria, la regulación de las respuestas a la hipoxia y la hipoglucemia.
- El ARNT juega un papel vital en la angiogénesis, potencialmente a través del factor de crecimiento endotelial vascular.
- Se propone un modelo en el que la activación de ARNT promueve la vascularización durante la organogénesis.
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