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The association of dynamin 2 with Rac1 plays an important role in NAD(P)H oxidase activation by angiotensin II in vascular smooth muscle cells
Author(s) -
Si Shuyi,
Su Lianfang,
He Xiaobo,
Jiang Wei,
Xiao Chunling,
Zuo L.
Publication year - 2007
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.21.6.a1149-c
Subject(s) - dynamin , nad+ kinase , angiotensin ii , microbiology and biotechnology , chemistry , rac1 , phosphorylation , reactive oxygen species , protein kinase b , nad(p)h oxidase , vascular smooth muscle , nadph oxidase , biochemistry , signal transduction , biology , endocrinology , endocytosis , receptor , enzyme , smooth muscle
OBJECTIVE: We tested the hypothesis that dynamin 2 associates with the small GTPase Rac1, a subunit of NAD(P)H oxidase, enabling NAD(P)H oxidase activation, and assessed whether these actions influence reactive oxygen species (ROS) generation and signaling by angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Immunfluorescence confocal microscopy indicated dynamin 2 was colocalized with Rac1 at basal conditions. After Ang II stimulation, co‐immunoprecipitation studies clearly showed that the association of dynamin 2 with Rac1 was enhanced, suggesting the association between dynamin2 and Rac1 play an important role in Ang II signaling. It has been demonstrated that Rac1 movement from the cytosol to the membrane by Ang II is a critical step for NAD(P)H oxidase activation in VSMCs. Here we showed dynamin 2 siRNA significantly inhibited Rac1 movement after Ang II stimulation, which thereby strongly blocked Ang II‐induced H 2 O 2 production by DCFDA fluorescence observation. Moreover, dynamin 2 siRNA significantly inhibited Ang II‐stimulated redox‐sensitive Akt phosphorylation without affecting redox‐insensitive ERK1/2 phosphorylation. CONCLUSIONS: The association of dynamin 2 with Rac1 plays an important role in Ang II‐mediated site‐directed assembly of functionally active NAD(P)H oxidase, reactive oxygen species generation, and activation of redox‐sensitive Akt, but not ERK1/2. These novel findings demonstrate dynamin 2 is involved in NAD(P)H oxidase activation and redox signaling by Ang II in VSMCs.