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Prdx1 (peroxiredoxin 1) deficiency reduces cholesterol efflux via impaired macrophage lipophagic flux
- Source :
- Autophagy
- Publication Year :
- 2017
- Publisher :
- Taylor & Francis, 2017.
-
Abstract
- Oxidative stress activates macroautophagy/autophagy and contributes to atherogenesis via lipophagic flux, a form of lipid removal by autophagy. However, it is not known exactly how endogenous antioxidant enzymes are involved in lipophagic flux. Here, we demonstrate that the antioxidant PRDX1 (peroxiredoxin 1) has a crucial role in the maintenance of lipophagic flux in macrophages. PRDX1 is more highly expressed than other antioxidant enzymes in monocytes and macrophages. We determined that Prdx1 deficiency induced excessive oxidative stress and impaired maintenance of autophagic flux in macrophages. Prdx1-deficient macrophages had higher intracellular cholesterol mass and lower cholesterol efflux compared with wild type. This perturbation in cholesterol homeostasis was due to impaired lipophagic cholesterol hydrolysis caused by excessive oxidative stress, resulting in the inhibition of free cholesterol formation and the reduction of NR1H3 (nuclear receptor subfamily 1, group H, member 3) activity. Notably, impairment of both lipophagic flux and cholesterol efflux was restored by the 2-Cys PRDX-mimics ebselen and gliotoxin. Consistent with this observation, apoe −/− mice transplanted with bone marrow from prdx1−/−apoe−/− mice had increased plaque formation compared with apoe−/− BM-transplanted recipients. This study reveals that PRDX1 is crucial to regulating lipophagic flux and maintaining macrophage cholesterol homeostasis against oxidative stress. We suggest that PRDX1-dependent control of oxidative stress may provide a strategy for treating atherosclerosis and autophagy-related human diseases.
- Subjects :
- 0301 basic medicine
Apolipoprotein E
Antioxidant
medicine.medical_treatment
macrophage
Biology
Peroxiredoxin 1
medicine.disease_cause
03 medical and health sciences
chemistry.chemical_compound
Mice
peroxiredoxin 1
medicine
Autophagy
Animals
Humans
lipophagy
Molecular Biology
Cells, Cultured
Liver X Receptors
Mice, Knockout
Gliotoxin
Cholesterol
Ebselen
Macrophages
Cell Biology
Peroxiredoxins
Atherosclerosis
3. Good health
Cell biology
Oxidative Stress
030104 developmental biology
Biochemistry
chemistry
Oxidative stress
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 15548635 and 15548627
- Volume :
- 14
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Autophagy
- Accession number :
- edsair.doi.dedup.....2a5cdb6fcc8d8a1ce8d3d327c83fe994