eIF2α-Independent Inhibition of TNF-α-Triggered NF-κB Activation by Salubrinal

Biological & Pharmaceutical Bulletin
S NakajimaJian Yao

Abstract

Salubrinal is a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2α (eIF2α). In previous reports, salubrinal was shown to have the potential to inhibit the activation of nuclear factor-κB (NF-κB) by several stimuli. However, the effects of salubrinal on NF-κB signaling are largely unknown. In this study, we investigated whether and how salubrinal affects NF-κB activation induced by tumor necrosis factor (TNF)-α and interleukin (IL)-1β. We found that salubrinal selectively blocked TNF-α- but not IL-1β-induced activation of NF-κB. This inhibitory effect occurred upstream of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Further experiments revealed that salubrinal blocked TNF-α-triggered NF-κB activation independent of its action on eIF2α because knockdown of eIF2α by small interfering RNA (siRNA) did not reverse the inhibitory effect of salubrinal on NF-κB. Moreover, guanabenz, a selective inhibitor of the regulatory subunit of protein phosphatase (PP) 1, also preferentially inhibited TNF-α-triggered activation of NF-κB. These findings raise the possibility that salubrinal may selectively block TNF-α-triggered activation of the NF-κB pathway through inhibition...Continue Reading

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Citations

May 26, 2017·BioMed Research International·Lorenzo Romero-RamírezM Asunción Barreda-Manso
Dec 13, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Jiaye JiangYan Ke
Oct 7, 2017·Molecular Medicine Reports·Jianmin QiuGang Wu
Feb 19, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Daniela Correia da SilvaDavid M Pereira

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