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The PLA2 activity is required for Angiotensin II‐mediated Endothelial NADPH oxidase
Author(s) -
NGUYEN SU DUY,
CHATTERJEE SHAMPA,
FISHER ARON B
Publication year - 2010
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.24.1_supplement.785.5
Subject(s) - nadph oxidase , apocynin , reactive oxygen species , phospholipase a2 , chemistry , oxidative stress , angiotensin ii , peroxiredoxin , phospholipase , oxidase test , nad(p)h oxidase , peroxidase , superoxide , gpx1 , biochemistry , enzyme , glutathione peroxidase , superoxide dismutase , receptor
Peroxiredoxin 6 (Prdx6), an antioxidant enzyme with both GSH peroxidase and phospholipase A 2 (PLA 2 ) activities, plays a protective function against oxidative stress. Unexpectedly, we have found that ROS generation by NADPH oxidase activation is markedly diminished in cells lacking Prdx6. We thus hypothesized that Prdx6 is a necessary component of the NADPH oxidase complex. ROS production upon Angiotensin II‐induced NADPH oxidase activation was determined in isolated lungs and pulmonary microvascular endothelial cells (PMVEC) using ROS‐specific fluorophores, dihydrodichlorofluorescein diacetate, dihydroethidium, and amplex red. Ang II‐treated lungs and PMVEC from WT mice but not from Prdx6 −/− mice showed a significant increase in ROS formation that was attenuated by MJ33, a selective inhibitor of PLA 2 activity of Prdx6. Lysophosphatidylcholine treatment enhanced ROS generation in both wild‐type and Prdx6 −/− cells, an effect that was abolished by the NADPH oxidase inhibitor, apocynin. Transfection of Prdx6‐null PMVEC with construct only expressing Prdx6 PLA 2 activity, but not those expressing only Prdx6 peroxidase activity, partially rescued the ROS response. These results indicate that Prdx6 participates in NADPH oxidase activation and this mechanism is mediated through phospholipase A 2 activity of Prdx6.