Despite myriad challenges, clinicians see room for progress.
Image credit: Shutterstock/David Tadevosian.
New Research In
Physical Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
-
Contributed by Susumu Tonegawa
Abstract
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.
Footnotes
-
↵* To whom reprint requests should be addressed at: Center for Cancer Research, E17-346, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139. e-mail: kdposs{at}mit.edu.
ABBREVIATIONS
- Hmox,
- heme oxygenase;
- E12.5,
- embryonic day 12.5;
- MEFs,
- murine embryonic fibroblasts;
- LPS,
- lipopolysaccharide
- Accepted July 16, 1997.
- Copyright © 1997, The National Academy of Sciences of the USA
Reduced stress defense in heme oxygenase 1-deficient cells
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Using CRISPR, researchers showed that a region some used to label “junk DNA” has a major role in a rare genetic disorder.
Image credit: Nathan Devery.
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
A study demonstrates how two enzymes—MHETase and PETase—work synergistically to depolymerize the plastic pollutant PET.
Image credit: Aaron McGeehan (artist).