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Oscillatory fluid shear stress‐induced JNK activation via NADPH oxidase implicates mitochondrial superoxide production in endothelial cells
Author(s) -
Jen Nelson,
Takabe Wakako,
Li Rongsong,
Ai Lisong,
Hsiai Tzung K.
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.784.13
Subject(s) - apocynin , nadph oxidase , superoxide , reactive oxygen species , chemistry , oxidative stress , western blot , oxidase test , superoxide dismutase , microbiology and biotechnology , biochemistry , enzyme , biology , gene
Oscillatory fluid shear stress (OSS) increases vascular oxidative stress and induces endothelial cell dysfunction. In our previous study, we demonstrated that OSS induced superoxide generation via activation of NADPH oxidase enzyme system. In this study, we examined the effect of OSS on mitochondrial dysfunction. Using chemical inhibitors against NADPH oxidase (Apocynin) and JNK (SP600125), we demonstrated that OSS induced JNK activation via NADPH oxidase in bovine aortic endothelial cells (BAEC). JNK activation peaked at 1h following treatment of OSS (±3dyn/cm 2 ) by western blot analysis. Apocynin inhibited this induction and also inhibited OSS‐induced superoxide generation measured by dihydroethidium. We then examined the role of JNK activation in OSS‐induced mtO 2 ·− production by using MitoSox Red dye specific for mtO 2 ·− . We found that SP600125 inhibited ·− production as quantified by flow cytometry. OSS‐stimulated mtO 2 Our data suggests that OSS‐activated NADPH oxidase induces intra‐cellular superoxide production and activates JNK, which in turn induces mtO 2 ·− production.. This study is supported by NIH HL083015 and HL091302.