The mitochondrial thioredoxin system regulates nitric oxide-induced HIF-1alpha protein.
Free Radic Biol Med
; 44(1): 91-8, 2008 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-18045551
ABSTRACT
Hypoxia-inducible factor-1 (HIF-1), consisting of two subunits, HIF-1alpha and HIF-1beta, is a key regulator for adaptation to low oxygen availability, i.e., hypoxia. Compared to the constitutively expressed HIF-1beta, HIF-1alpha is regulated by hypoxia but also under normoxia (21% O(2)) by several stimuli, including nitric oxide (NO). In this study, we present evidence that overexpression of mitochondrial-located thioredoxin 2 (Trx2) or thioredoxin reductase 2 (TrxR2) attenuated NO-evoked HIF-1alpha accumulation and transactivation of HIF-1 in HEK293 cells. In contrast, cytosolic-located thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount and activity under NO treatments. Taking into consideration that thioredoxins affect the synthesis of HIF-1alpha by altering Akt/mTOR signaling, we herein show that p42/44 mitogen-activated protein kinase and p70S6 kinase are involved. Moreover, intracellular ATP was increased in Trx1-overexpressing cells but reduced in cells overexpressing Trx2 or TrxR2, providing thus an understanding of how protein synthesis is regulated by thioredoxins.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiorredoxinas
/
Activación Transcripcional
/
Proteínas Mitocondriales
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Tiorredoxina Reductasa 2
/
Óxido Nítrico
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania