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Overexpression of redox factor-1 negatively regulates NO synthesis and apoptosis in LPS-stimulated RAW 264.7 macrophages

2003; Wiley; Volume: 556; Issue: 1-3 Linguagem: Inglês

10.1016/s0014-5793(03)01361-9

1873-3468

Young Hyun Yoo, Young-Jin Lim, Sang Eun Park, Jong Min Kim, Young Chul Park,

Nitric Oxide and Endothelin Effects

Redox factor-1 (Ref-1) is a ubiquitously expressed protein with proven roles as a modulator of redox-sensitive transcription, and as an endonuclease in the base excision repair pathway of oxidatively damaged DNA. Although Ref-1 is induced by a variety of oxidative stress and protects cells against oxidative stress, the function of Ref-1 in regulating nitric oxide (NO) synthesis has not been elucidated to date. We investigated the role of Ref-1 in regulating NO synthesis and NO-mediated apoptosis employing adenoviral-mediated overexpression of Ref-1 in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. LPS treatment produced NO synthesis and NO-mediated apoptosis. Forced overexpression of Ref-1 suppressed LPS-stimulated NO synthesis. In parallel with this, Ref-1 also mitigated alteration of inducible NO synthase expression and NO-mediated apoptosis. Our findings suggest that Ref-1 is implicated in protection against cell death resulting from oxidative stimuli containing NO.