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The N‐terminal region of peroxiredoxin 6 determines its localization to lysosomal‐like structures in alveolar macrophages and A549 cells
Author(s) -
Sorokina Elena M.,
Wu Yongzheng,
Feinstein Sheldon I.,
Fisher Aron B.
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.20.4.a90
Subject(s) - lamellar granule , microbiology and biotechnology , chemistry , a549 cell , phospholipase a2 , alveolar epithelium , peroxiredoxin , pulmonary surfactant , biochemistry , epithelium , cell , biology , peroxidase , enzyme , genetics
Peroxiredoxin 6 (Prdx6), a bifunctional 25 kDa thiol‐specific antioxidant protein with both GSH peroxidase and phospholipase A2 (PLA2) activities, is highly expressed in human respiratory epithelium and when overexpressed protects against oxidative stress. The PLA2 activity of Prdx6 is Ca 2+ independent and maximal at acidic pH (aiPLA 2 ). Lung surfactant phospholipids are endocytosed by alveolar epithelial cells and are degraded in lysosomes by phospholipase A2. Deletion of Prdx6 markedly diminishes lung surfactant phospholipid degradation and its re‐synthesis by the reacylation pathway. Prdx6 has been localized by sub‐cellular fractionation to lung lamellar bodies and lysosomes. In this study using immunofluorescence, we demonstated Prdx6 co‐localization with Lamp‐1, a lysosomal marker, in alveolar macrophages. Using GFP‐labeled protein expression in A549 cells, a cell line derived from lung epithelium,we showed that the N‐terminal 120 amino acids of the protein are sufficient for its localization to small organellar structures compatible with lysosomes. These studies suggest that the Prdx6 N‐terminal region may contain a targeting sequence that is responsible for its lysosomal localization and consequent PLA2 activity. This work was supported by R01 HL 075587.