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Hyperoxia upregulates Egr‐1 expression in cultured alveolar cells
Author(s) -
Agani Faton H,
Jones Nicole
Publication year - 2006
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.20.5.lb40
Subject(s) - hyperoxia , mapk/erk pathway , wortmannin , downregulation and upregulation , blot , microbiology and biotechnology , signal transduction , chemistry , pi3k/akt/mtor pathway , biology , biochemistry , gene , organic chemistry , oxygen
Early growth response gene (Egr‐1) is a stress response gene, activated by forms of stress and growth factor signaling. In mouse alveolar cells LA4, hyperoxia increased Egr‐1 mRNA expression and protein content. Hyperoxia also activated EGR‐Luc reporter gene. Blockade of MEK signaling prevented Egr‐1 activation by hyperoxia. When cells were pretreated for 30 min with inhibitors of MEK/ERK pathway (PD 98059; 50 μM), p38 pathway (SB 203580; 10μM) and inhibitor of PI3K Wortmannin (100 nM), followed by 1 h hyperoxia and Northern blotting, only PD98059 prevented Egr‐1 upregulation. Hyperoxia further phosphorylated ERK ½ kinase as demonstrated by Western blotting performed with phosphospecific antibodies against phosphor‐ ERK ½. Treatment of LA4 cells with EGFR specific inhibitors PD 153035 and 158780 blocked Egr1 mRNA upregulation. These results suggest that EGFR signaling mediates Egr‐1 activation during hyperoxia. It remains to be established what are the downstream targets of Egr‐1 and how does Egr‐1 activation affect cellular adaptations and survival during hyperoxia.