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

Jun Song1, Jing Li, Jingbo Qiao

  • 1Department of Surgery, The University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0353, USA.

Biochemical and Biophysical Research Communications
|December 9, 2008
PubMed

Insights

Protein kinase D (PKD) protects intestinal cells from hydrogen peroxide (H2O2)-induced death by regulating nuclear factor-kappaB (NF-kappaB) and p38 mitogen-activated protein kinase (MAPK) pathways.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of cell death
  • Signal transduction pathways

Background:

  • Protein kinase D (PKD) has a demonstrated protective role in intestinal cells against hydrogen peroxide (H2O2)-induced cell death.
  • The precise molecular mechanisms underlying PKD's protective function remain to be fully elucidated.

Purpose of the Study:

  • To investigate the involvement of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs) in mediating the protective effects of PKD against H2O2-induced intestinal cell death.
  • To determine how PKD interacts with NF-kappaB and specific MAPK pathways, including p38 MAPK, extracellular signal-regulated kinases (ERK1/2), and c-Jun N-terminal kinases (JNK).

Main Methods:

  • Utilized RIE-1 cells for experimental models.
  • Employed small interfering RNA (siRNA) targeting PKD1 to inhibit its expression.
  • Overexpressed wild-type and kinase-dead forms of PKD1.
  • Assessed NF-kappaB activation, p65 translocation, and IkappaB-alpha phosphorylation.
  • Measured the phosphorylation status of p38 MAPK, MKK3/6, ERK1/2, and JNK.

Main Results:

  • H2O2 treatment activated NF-kappaB, including p65 translocation and IkappaB-alpha phosphorylation in RIE-1 cells.
  • PKD1 siRNA significantly inhibited H2O2-induced NF-kappaB activation and IkappaB-alpha phosphorylation.
  • Overexpression of wild-type PKD1 attenuated H2O2-induced phosphorylation of p38 MAPK and its activators (MKK3/6).
  • Conversely, PKD1 siRNA or kinase-dead PKD1 enhanced p38 MAPK and MKK3/6 phosphorylation.
  • PKD modulation did not affect the phosphorylation of ERK1/2 or JNK.

Conclusions:

  • PKD protects intestinal cells from H2O2-induced cell death.
  • This protection is mediated, in part, by the up-regulation of NF-kappaB signaling.
  • PKD exerts its protective effect through the down-regulation of the p38 MAPK pathway.

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