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NF‐κB and AP‐1 differentially contribute to the induction of Mn‐SOD and eNOS during the development of oxidant tolerance
Author(s) -
Rui Tao,
Kvietys Peter R.
Publication year - 2005
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/fj.05-4028fje
Subject(s) - enos , transcription factor , microbiology and biotechnology , chromosomal translocation , myocyte , chemistry , nf κb , pro oxidant , nfkb1 , biology , signal transduction , nitric oxide synthase , reactive oxygen species , biochemistry , enzyme , gene
Exposure of cardiac myocytes to anoxia/reoxygenation (A/R) increases myocyte oxidant stress and converts the myocytes to a proinflammatory phenotype. These oxidant‐induced effects are prevented by pretreatment of the myocytes with an oxidant stress (A/R or H 2 O 2 ) 24 h earlier (oxidant tolerance). Although NF‐κB and AP‐1 (nuclear signaling) and Mn‐SOD and eNOS (effector enzymes) have been implicated in the development oxidant tolerance, the precise relationship between the nuclear transcription factors and the effector enzymes in the development of oxidant tolerance has not been defined. Herein, we show that an initial A/R challenge results in nuclear accumulation of both NF‐κB and AP‐1 (EMSA). In addition, blockade of nuclear translocation of NF‐κB (SN50) or AP‐1 (decoy oligonucleotide) prevents the development of oxidant tolerance, i.e., the second A/R challenge produces the same quantitative effects as the initial A/R challenge. In this model, nuclear translocation of both NF‐κB and AP‐1 is required for induction of Mn‐SOD, while nuclear translocation of AP‐1, but not NF‐κB, is a prerequisite for induction of eNOS. Collectively, our findings indicate that NF‐κB and AP‐1 work in concert to ensure the induction eNOS and Mn‐SOD, which in turn are important for the development of oxidant tolerance.