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Angiotensin II stimulates neural stem cell proliferation through Nox4‐generated superoxide
Author(s) -
Topchiy Elena,
Panzhinskiy Evgeniy,
Das Mita,
Zawada Michael
Publication year - 2011
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.25.1_supplement.lb521
Subject(s) - nox4 , superoxide , nadph oxidase , neural stem cell , reactive oxygen species , angiotensin ii , microbiology and biotechnology , chemistry , oxidative stress , neurogenesis , cell growth , superoxide dismutase , mitochondrion , stem cell , biology , biochemistry , receptor , enzyme
How reactive oxygen species (ROS) affect neural stem cell (NSC) self‐renewal is poorly understood, but might be important for normal development and during neurodegenerative conditions. We investigated whether production of superoxide via activation of NADPH oxidase (Nox) affects NSC proliferation. In the vascular smooth muscle cells, angiotensin II (Ang II) activates Nox‐driven superoxide generation to induce proliferation. We hypothesized that Ang II activates one of the Nox isoforms to regulate NSC self‐renewal. In a murine neural stem cell line, C17.2, Ang II (100nM) stimulated superoxide production detected by dihydroethidium (DHE) fluorescence. Ang II increased proliferation and an antioxidant N‐acetyl‐cysteine blocked Ang II‐induced increase in cell numbers. Confocal microscopy using DHE and a mitochondrial marker (MitoTracker) revealed that C17.2 cells contain two sources of ROS: mitochondrial and extramitochondrial, indicating that Nox might be involved. Nox4 was found to be constitutively expressed and Ang II increased protein levels of Nox4. SiRNA targeting Nox4 reduced Nox4 expression and attenuated Ang II‐induced ROS production and proliferation. Our findings suggest that Ang II‐induced proliferation of NSCs requires Nox4‐generated superoxide production. This mechanism might be important for normal and stress‐ or disease‐modified neurogenesis. Support: AA016654 and HL64917.