Dual role of peroxiredoxin I in macrophage-derived foam cells.
J Biol Chem
; 281(38): 27991-8001, 2006 Sep 22.
Article
en En
| MEDLINE
| ID: mdl-16880205
ABSTRACT
We and others have shown that foam cell formation initiated by exposing macrophages to oxidized low density lipoprotein (oxLDL) triggers the differential expression of a number of proteins. Specifically, our experiments have identified peroxiredoxin I (Prx I) as one of these up-regulated proteins. The peroxiredoxins, a family of peroxidases initially described for their antioxidant capability, have generated recent interest for their potential to regulate signaling pathways. Those studies, however, have not examined peroxiredoxin for a potential dual functionality as both cytoprotective antioxidant and signal modulator in a single, oxidant-stressed system. In this report, we examine the up-regulation of Prx I in macrophages in response to oxLDL exposure and its ability to function as both antioxidant enzyme and regulator of p38 MAPK activation. As an antioxidant, induction of Prx I expression led to improved cell survival following treatment with oxLDL or tert-butyl hydroperoxide. The improved survival coincided with a decrease in measurable reactive oxygen species (ROS), and both the increased survival and reduced ROS were reversed by Prx I small interfering RNA transfection. Additionally, our data show that activation of p38 MAPK in oxLDL-treated macrophages was dependent on the up-regulation of Prx I. Reduction of Prx I expression by small interfering RNA transfection resulted in a significant decrease in p38 MAPK activation, whereas the up-regulation of Prx I expression with either oxLDL or ethoxyquin led to increased p38 MAPK activation. These results are consistent with multiple roles for Prx I in macrophage-derived foam cells that include functionality as both an antioxidant and a regulator of oxidant-sensitive signal transduction.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peroxidasas
/
Células Espumosas
/
Proteínas de Choque Térmico
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos