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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
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¿Se requiere SIRT2 para la necroptosis?
Kim Newton1, Joanne M Hildebrand2, Zhirong Shen3
1Genentech, Inc., South San Francisco, California 94080, USA.
Nature
|February 28, 2014
Resumen
Este estudio investigó el papel de SIRT2 en la necroptosis, una forma de muerte celular programada. Los investigadores descubrieron que la inhibición o eliminación de SIRT2 no protegía a las células de la necroptosis, lo que cuestiona su importancia en esta vía.
Área de la Ciencia:
- Biología celular Biología celular.
- Los mecanismos moleculares de la muerte celular.
Sus antecedentes:
- Las sirtuinas, una clase de proteínas, regulan los procesos celulares a través de la desacetilación.
- Investigaciones anteriores sugirieron que SIRT2 es esencial para la necroptosis, una vía regulada de muerte celular.
Objetivo del estudio:
- Confirmar e investigar el papel de la SIRT2 en la necroptosis.
- Desafiar la hipótesis existente sobre el requisito de SIRT2 para la necroptosis.
Principales métodos:
- Utilizó múltiples inhibidores de SIRT2 (AGK2) y técnicas de silenciamiento de genes (siRNAs).
- Se emplearon modelos de ratones knockout (Sirt2-/-) y controles de tipo salvaje.
- Se evaluó la muerte celular en respuesta a la inducción del factor de necrosis tumoral (TNF) y el síndrome de respuesta inflamatoria sistémica (SIRS).
Principales resultados:
- La inhibición o el agotamiento de la SIRT2 no confiere protección contra la necroptosis.
- Los ratones Sirt2-/- exhibieron una mayor susceptibilidad al SIRS inducido por el TNF en comparación con los ratones de tipo salvaje.
- Los ratones con deficiencia de Ripk3 (Ripk3-/-) fueron resistentes a la necroptosis, sirviendo como un control positivo.
Conclusiones:
- Los hallazgos desafían el papel establecido de SIRT2 en la vía de la necroptosis.
- SIRT2 puede no ser un regulador crítico de la necroptosis como se sugirió anteriormente.
- Se necesitan más investigaciones para aclarar completamente la función de SIRT2 en la muerte celular.
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