Okadaic acid activates the PKR pathway and induces apoptosis through PKR stimulation in MG63 osteoblast-like cells

Haneji,Tatsuji; Hirashima,Kanji; Teramachi,Jumpei; Morimoto,Hiroyuki

doi:10.3892/ijo.2013.1911

Okadaic acid activates the PKR pathway and induces apoptosis through PKR stimulation in MG63 osteoblast-like cells

Authors:
- Tatsuji Haneji
- Kanji Hirashima
- Jumpei Teramachi
- Hiroyuki Morimoto
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Affiliations: Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima 770-8504, Japan, Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Yahatanishi, Kitakyushu 807-8555, Japan
Published online on: April 17, 2013 https://doi.org/10.3892/ijo.2013.1911
Pages: 1904-1910
Copyright: © Haneji et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Double-stranded RNA-dependent protein kinase (PKR) is one of the players in the cellular antiviral responses and is involved in transcriptional stimulation through activation of NF-κB. Treatment of the human osteosarcoma cell line MG63 with the protein phosphatase inhibitor okadaic acid stimulated the expression and phosphorylation of IκBα, as judged from the results of real-time PCR and western blot analysis. We investigated the functional relationship between PKR and signal transduction of NF-κB by establishing PKR-K/R cells that produced a catalytically inactive mutant of PKR. Phosphorylation of eIF-2α, a substrate of PKR, was not stimulated by okadaic acid in the PKR-K/R cells, whereas okadaic acid induced phosphorylation of eIF-2α in MG63 cells. Phosphorylation of NF-κB in MG63 cells was stimulated by okadaic acid; however, okadaic acid did not induce phosphorylation of NF-κB in the PKR-K/R cells. Finally, okadaic acid-induced apoptosis was inhibited in the PKR-K/R cells. Our results suggest that okadaic acid-induced phosphorylation of IκBα was mediated by PKR kinase activity, thus, indicating the involvement of this kinase in the control mechanism governing the activation of NF-κB and induction of apoptosis.

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