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Peroxiredoxins as Mechanosensitive Antioxidants in a Subcellular‐Specific Manner
Author(s) -
Mowbray Amy L.,
Kang Sang Won,
Jo Hanjoong
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1453-a
Subject(s) - reactive oxygen species , mechanosensitive channels , subcellular localization , microbiology and biotechnology , colocalization , cytoplasm , chemistry , immunofluorescence , nadph oxidase , oxidative stress , biology , biochemistry , immunology , ion channel , antibody , receptor
Atherosclerotic lesions colocalize with areas of disturbed flow in the arteries. We showed that oscillatory shear stress (OS) increases reactive oxygen species (ROS) in endothelial cells (ECs) in an NADPH oxidase‐dependent manner. In contrast, laminar shear stress (LS) reduces ROS via an unknown mechanism. Peroxiredoxins (PRX) are antioxidant proteins that reduce H 2 O 2 , but their role in atherogenesis is unclear. We hypothesize that shear stress regulates ROS in ECs by controlling PRX. To test this hypothesis, mouse aortic endothelial cells (MAECs) were subjected to static, laminar, and oscillatory culture conditions. Immunoblots and immunofluorescence were used to assess the expression and localization of mammalian peroxiredoxins (PRX I‐VI). Immunoblots indicated that LS upregulated PRX I, III, IV, and VI levels significantly above static controls. Immunofluorescence also showed a distinct subcellular localization of each PRX: PRX I, II, V and VI in the cytoplasm, PRX I and V in the Golgi, PRX III, IV, and V in the mitochondria, and PRX IV in the plasma membrane. These results indicate that peroxiredoxins are mechanosensitive antioxidants, removing ROS in a subcellular‐specific manner. We suggest that anti‐inflammatory and anti‐atherogenic effects of shear stress are mediated by exquisite regulation of ROS in subcellular organelles. Supported by NIH HL67413, PO1HL075209 (HJ)