Premium
PGA2‐induced Heme Oxygenase‐1 Expression Requires both p38 MAPK and de novo Protein Synthesis in U2OS cells.
Author(s) -
Ko KyoungWon,
Choe YunJung,
Jeong SeongWhan,
Kim HoShik
Publication year - 2010
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.24.1_supplement.485.12
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , heme oxygenase , chemistry , microbiology and biotechnology , transfection , cycloheximide , protein kinase a , signal transduction , phosphorylation , biology , heme , biochemistry , protein biosynthesis , enzyme , gene
Previous studies have shown that PGA2 induces antioxidant enzyme heme oxygenase‐1 (HO‐1) expression, but the mechanism involved has not been fully understood. In this study, we suggest the signal transduction pathway of PGA2‐induced HO‐1 expression in human osteosarcoma (U2OS) cells. HO‐1 expression was induced by PGA2 (20 ug/ml) treatment for 8 hr in U2OS cells. Parallel to HO‐1 expression, p38 MAPK and p44/42 MAPK were phosphorylated by PGA2. PGA2‐mediated HO‐1 expression was completely reduced by p38 MAPK inhibitor (SB203580) as well as cycloheximide, while inhibition of p44/42 MAPK using U0126 and PD98059 had no effect. To elucidate a role of p38 MAPK in the induction of HO‐1 by PGA2, constitutively active form of MKK6 (CA‐MKK6), the upstream activator of p38 MAPK, was co‐transfected with p38 MAPK into U2OS cells. In these cells, p38 MAPK was phosphorylated by CA‐MKK6 but HO‐1 was not induced, indicating that p38 MAPK activation is not sufficient for HO‐1 expression. Taken together, our findings suggest that PGA2 induces expression of HO‐1 via cooperative action of p38 MAPK and de novo synthesis of (an) unidentified protein(s). This research was supported by MRC from cell death disease research center funded by KOSEF.