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Measurement of Heme Synthesis Levels in Mammalian Cells
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Regulación nutricional de la biosíntesis hepática del hemo y la porfiria a través del PGC-1alpha
Christoph Handschin1, Jiandie Lin, James Rhee
1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|August 27, 2005
Resumen
El coactivador gamma 1alfa del receptor activado por el proliferador peroxisomático (PGC-1alpha) vincula el estado nutricional con la biosíntesis del hemo. Este hallazgo explica cómo el ayuno desencadena los ataques de porfiria hepática aguda y ofrece nuevos objetivos terapéuticos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Genética La genética.
- Trastornos metabólicos Los trastornos metabólicos son trastornos metabólicos que se producen en el cuerpo.
Sus antecedentes:
- Las porfirías hepáticas inducibles son trastornos hereditarios de la biosíntesis del hemo.
- Los ataques agudos incluyen síntomas neuropsiquiátricos y aumento de la excreción de ácido delta-aminolevulínico (ALA).
- Los desencadenantes incluyen medicamentos, hormonas y ayuno; las infusiones de glucosa y hemo son tratamientos, pero los mecanismos no están claros.
Objetivo del estudio:
- Para investigar el papel de PGC-1alpha en la regulación de la biosíntesis del hemo.
- Para aclarar los mecanismos que vinculan el ayuno y los ataques de porfiria.
- Para identificar el PGC-1alpha como un potencial objetivo terapéutico.
Principales métodos:
- Elevación mediada por el vector adenoviral de PGC-1alfa en ratones.
- Análisis de los niveles de precursores del hemo in vivo.
- Evaluación de la inducción de ALAS-1 en ayunas y efectos farmacológicos en ratones PGC-1alpha knockout específicos del hígado.
Principales resultados:
- Los niveles elevados de PGC-1alfa aumentaron los precursores de hemo, imitando los ataques de porfiria aguda.
- La regulación al alza de la ALAS-1 inducida por el ayuno fue abolida en ratones con deficiencia de PGC-1alfa.
- Los efectos de los fármacos porfirogénicos en la biosíntesis del hemo se perdieron en ratones con deficiencia de PGC-1alfa.
Conclusiones:
- PGC-1alpha actúa como un vínculo crucial entre el estado nutricional y la biosíntesis del hemo.
- PGC-1alpha media el impacto del ayuno en el metabolismo del hemo.
- Comprender el papel de PGC-1alpha proporciona información sobre la patogénesis y el tratamiento de la porfiria hepática aguda.
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