PKD prevents H2O2-induced apoptosis via NF-κB and p38 MAPK in RIE-1 cells

Jun Song, Jing Li, Jingbo Qiao, Sunil Jain, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Previously, we demonstrated that protein kinase D (PKD) plays a protective role during H2O2-induced intestinal cell death. Here, we sought to determine whether this effect is mediated by nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Treatment with H2O2 activated NF-κB in RIE-1 cells; H2O2 also induced the translocation of NF-κB p65 as well as phosphorylation of IκB-α. PKD1 siRNA inhibited H2O2-induced activation, translocation of NF-κB, and phosphorylation of IκB-α. We also found that overexpression of wild type PKD1 attenuated H2O2-induced phosphorylation of p38 MAPK and its upstream activator, MAPK kinase (MKK) 3/6, whereas the phosphorylation was increased by PKD1 siRNA or kinase-dead PKD1. Phosphorylation of neither extracellular signal-regulated kinases (ERK) 1/2 nor c-Jun N-terminal kinases (JNK) was altered by PKD1 plasmids or siRNA. Our findings suggest that PKD protects intestinal cells through up-regulation of NF-κB and down-regulation of p38 MAPK.

Original languageEnglish
Pages (from-to)610-614
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume378
Issue number3
DOIs
StatePublished - Jan 16 2009

Bibliographical note

Funding Information:
The authors thank Karen Martin for manuscript preparation and Tatsuo Uchida for assistance with statistical analyses. This work was supported by the Grants RO1 DK61470, RO1 DK48498, RO1 CA104748, PO1 DK 35608 from the National Institutes of Health and a Grant #8580 from the Shriners Hospital for Children.

Keywords

  • NF-κB
  • Oxidative stress
  • Protein kinase D
  • p38 MAPK

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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