Cytosolic Peroxiredoxin Attenuates The Activation Of Jnk And P38 But Potentiates That Of Erk In Hela Cells Stimulated With Tumor Necrosis Factor-α

With the use both of HeLa cells expressing wild-type or dominant negative forms of the cytosolic peroxidase peroxiredoxin II and of mouse embryonic fibroblasts deficient in this protein, we evaluated the roles of H2O2 in the activation of mitogen-activated protein kinase by TNF-␣

Sang Won Kang; Tong-Shin Chang; Tae-Hoon Lee; Eun Seon Kim; Dae-Yeul Yu; Sue Goo Rhee

2004

Scholarcy highlights

  • Tumor necrosis factor-␣ induces the activation of all three types of mitogen-activated protein kinase: c-Jun NH2-terminal kinase, p38, and extracellular signal-regulated kinase. This cytokine induces the production of several types of reactive oxygen species, including H2O2. With the use both of HeLa cells expressing wild-type or dominant negative forms of the cytosolic peroxidase peroxiredoxin II and of mouse embryonic fibroblasts deficient in this protein, we evaluated the roles of H2O2 in the activation of MAPKs by TNF-␣
  • In vitro kinase assays as well as immunoblot analysis with antibodies specific for activated MAPKs indicated that H2O2 produced in response to TNF-␣ potentiates the activation of JNK and p38 induced by this cytokine but inhibits that of ERK
  • TNF-␣ is an extracellular stimulus that induces the production in cells of O2., H2O2, and NO, all of which in turn are thought to participate in intracellular signaling pathways activated by this cytokine
  • MAPK signaling cascades are regulated both directly and indirectly by reactive oxygen species, and the aim of the present study was to determine the role of H2O2 in the TNF␣-induced activation of individual MAPKs as well as to evaluate that of a cytosolic Prx in TNF-␣ signaling pathways
  • When similar kinase assays were carried out with CT4, WT12, and DN15, TNF-alpha-induced ERK activation was ϳ40% higher in WT12 cells but was ϳ40% lower in DN15 cells compared with that apparent in CT4 cells
  • Among the various oxidants produced in cells, catalase removes H2O2 selectively, overexpression of this enzyme has been used to study the role of H2O2 in signaling pathways triggered by several stimulants
  • In agreement with the previous findings, we observed that the TNF-␣-induced activation of ASK1 was inhibited in cells overexpressing wild-type Prx II but was increased in cells expressing dominant negative Prx II

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