Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury

Jun Song, Jing Li, Joshua M. Mourot, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK)ζ, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGKζ siRNA transfection decreased H2O2-induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGKζ also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGKζ rapidly translocated to the cytoplasm following H2O2 treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGKζ, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells.

Original languageEnglish (US)
Pages (from-to)200-204
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume375
Issue number2
DOIs
StatePublished - Oct 17 2008
Externally publishedYes

Keywords

  • DGK
  • Intestinal epithelial cells
  • PKD
  • ROS

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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