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Ambient ultrafine particles (UFP) inhibit eNOS activity via S‐glutathionylation
Author(s) -
Hill James,
Shen Melody,
Li Rongsong,
Ning Zhi,
Sioutas Constantinos,
Hsiai Tzung
Publication year - 2012
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.26.1_supplement.573.8
Subject(s) - enos , oxidative stress , nitric oxide , chemistry , ultrafine particle , immunology , endocrinology , biochemistry , medicine , nitric oxide synthase , organic chemistry
Atherosclerosis is a systemic disease, and its development is dependent upon a complex interplay among numerous genetic, epigenetic, and environmental risk factors. It is increasingly recognized that ambient UFP exposure promotes vascular oxidative stress and inflammatory responses. In this study, we tested the hypothesis that UFP attenuates eNOS activity via S‐glutathionylaiton. Treatment of human aortic endothelial cells (HAEC) with ambient UFP (Dp<100nm) significantly inhibited nitric oxide (NO) production as measured by Griess assay (Control: 3.645, UFP: 1.662, P<.01, n=4). To assess whether oxidative stress induced eNOS uncoupling via S‐glutathionylation, we demonstrated that UFP treatment increased eNOS S‐glutathionylation in HAEC by a modified ELISA procedure. To inhibit S‐glutahionylation, we over‐expressed glutaredoxin‐1 (Grx‐1), and showed a significant attenuation of UFP‐mediated decrease in NO production (LacZ+UFP: .338, Grx1+UFP: .630, P<.01, n=6). Thus, our findings suggest that UFP inhibited eNOS activity via an increase in S‐ glutathionylation.