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La ferroportina eritrocítica reduce la acumulación intracelular de hierro, la hemólisis y el riesgo de malaria
De-Liang Zhang1, Jian Wu2, Binal N Shah3
1Section on Human Iron Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Science (New York, N.Y.)
|March 31, 2018
Resumen
La ferroportina exportadora de hierro (FPN) protege los glóbulos rojos de la malaria. Una mutación específica de FPN (Q248H) encontrada en poblaciones africanas ofrece protección contra la malaria severa, destacando el papel de FPN en la resistencia a la enfermedad.
Área de la Ciencia:
- Hematología
- Parasitología
- La genética
Sus antecedentes:
- La infección por malaria interrumpe la regulación del hierro y causa anemia en los humanos.
- Paradójicamente, la suplementación con hierro empeora la malaria, pero el mecanismo subyacente no está claro.
- Los glóbulos rojos (glóbulos rojos) son fundamentales para la patogénesis de la malaria y el metabolismo del hierro.
Objetivo del estudio:
- Investigar el papel de la ferroportina exportadora de hierro (FPN) en los glóbulos rojos durante la infección por malaria.
- Comprender cómo la función de la FPN y las variaciones genéticas influyen en la gravedad de la malaria y la defensa del huésped.
Principales métodos:
- Eliminación condicional del gen FPN en las células eritroides de ratones.
- Análisis de la expresión y actividad de FPN en glóbulos rojos.
- Investigación de una mutación prevalente de la FPN humana (Q248H) y su efecto sobre la degradación de la FPN y la protección contra la malaria.
Principales resultados:
- FPN es abundante en glóbulos rojos y su actividad es suprimida por la suplementación de hierro.
- La eliminación de FPN en las células eritroides conduce a una sobrecarga de hierro, daño celular, hemólisis y aumento de la mortalidad en ratones infectados por malaria.
- La mutación humana FPN Q248H previene la degradación inducida por la hepcidina, lo que confiere protección contra la malaria grave.
- La evidencia sugiere una selección positiva de FPN Q248H en poblaciones africanas debido a la presión de la malaria.
Conclusiones:
- La ferroportina (FPN) desempeña un papel protector crítico en los glóbulos rojos contra el estrés oxidativo y la malaria.
- La mutación FPN Q248H confiere una protección significativa contra la malaria severa y ha sido seleccionada en regiones endémicas de malaria.
- Comprender el papel de la FPN ofrece información sobre la patogénesis de la malaria y las posibles estrategias terapéuticas.
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