Overexpression of redox factor-1 negatively regulates NO synthesis and apoptosis in LPS-stimulated RAW 264.7 macrophages.
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.
Yoo
Young Hyun
YH
Department of Anatomy and Cell Biology, Dong-A University College of Medicine (BK21 Program), 602-714, Pusan, South Korea.
Lim
Young-Jin
YJ
Park
Sang Eun
SE
Kim
Jong Min
JM
Park
Young Chul
YC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D019076:Transgenes
D008070:Lipopolysaccharides; D009573:Nitrites; D011994:Recombinant Proteins; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C085108:APEX1 protein, human; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase