Reduced stress defense in heme oxygenase 1-deficient cells
AUTOR(ES)
Poss, Kenneth D.
FONTE
The National Academy of Sciences of the USA
RESUMO
Stressed mammalian cells up-regulate heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells from mice lacking functional Hmox1 to oxidative challenges. Cultured Hmox1−/− embryonic fibroblasts demonstrated high oxygen free radical production when exposed to hemin, hydrogen peroxide, paraquat, or cadmium chloride, and they were hypersensitive to cytotoxicity caused by hemin and hydrogen peroxide. Furthermore, young adult Hmox1−/− mice were vulnerable to mortality and hepatic necrosis when challenged with endotoxin. Our in vitro and in vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23533Documentos Relacionados
- Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice
- Leydig cell–derived heme oxygenase-1 regulates apoptosis of premeiotic germ cells in response to stress
- Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency
- High-Mobility Group Box 1 Contributes to Lethality of Endotoxemia in Heme Oxygenase-1–Deficient Mice
- Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts.