TXNIP maintains the hematopoietic cell pool by switching the function of p53 under oxidative stress.
Cell Metab
; 18(1): 75-85, 2013 Jul 02.
Article
en En
| MEDLINE
| ID: mdl-23823478
ABSTRACT
Reactive oxygen species (ROS) are critical determinants of the fate of hematopoietic stem cells (HSCs) and hematopoiesis. Thioredoxin-interacting protein (TXNIP), which is induced by oxidative stress, is a known regulator of intracellular ROS. Txnip(-/-) old mice exhibited elevated ROS levels in hematopoietic cells and showed a reduction in hematopoietic cell population. Loss of TXNIP led to a dramatic reduction of mouse survival under oxidative stress. TXNIP directly regulated p53 protein by interfering with p53- mouse double minute 2 (MDM2) interactions and increasing p53 transcriptional activity. Txnip(-/-) mice showed downregulation of the antioxidant genes induced by p53. Introduction of TXNIP or p53 into Txnip(-/-) bone marrow cells rescued the HSC frequency and greatly increased survival in mice following oxidative stress. Overall, these data indicate that TXNIP is a regulator of p53 and plays a pivotal role in the maintenance of the hematopoietic cells by regulating intracellular ROS during oxidative stress.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tiorredoxinas
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Células Madre Hematopoyéticas
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Transducción de Señal
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Proteínas Portadoras
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Proteína p53 Supresora de Tumor
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Estrés Oxidativo
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Hematopoyesis
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2013
Tipo del documento:
Article