A pathway involving protein kinase Cδ up-regulates cytosolic phospholipase A 2α in airway epithelium

Hye Jin You, Jee Won Lee, Yung Joon Yoo, Jae-Hong Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cytosolic phospholipase A 2α (cPLA 2α) catalyzes the hydrolysis of glycerophospholipids at the sn-2 position to liberate fatty acids. Although cPLA 2α has been implicated in various cellular processes, the detailed mechanism of its expression remains to be elucidated. Here we report that phorbol 12-myristate 13-acetate (PMA) up-regulates cPLA 2α in A549 airway epithelium cells, and that this effect is sensitive to rottlerin, a potent inhibitor of protein kinase Cδ (PKCδ). Consistent with this observation, a dominant negative mutant of PKCδ reduced cPLA 2α induction in response to PMA. Up-regulation of cPLA 2α by PMA was also inhibited by PDTC, an inhibitor of nuclear factor-kappa B (NF-κB), and degradation of IκB and subsequent activation of NF-κB occurred in response to PMA treatment. These findings indicate that PMA induces expression of cPLA 2α at the transcriptional level via an NF-κB-dependent mechanism. In addition, activation of the NF-κB promoter by PMA was diminished by pretreatment with DPI, a flavoenzyme inhibitor as well as by rottlerin, suggesting a role for reactive oxygen species (ROS) as well as PKCδ. Consistent with this, PMA stimulated the production of ROS and this was blocked by inhibiting PKCδ. Our results suggest that PKCδ and ROS lie upstream of NF-κB, and we conclude that a PKCδ-ROS-NF- κB cascade plays a pivotal role in cPLA 2α induction by PMA.

Original languageEnglish
Pages (from-to)657-664
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume321
Issue number3
DOIs
Publication statusPublished - 2004 Aug 27

Fingerprint

Phospholipases A
Protein Kinase C
Acetates
Up-Regulation
Epithelium
NF-kappa B
Reactive Oxygen Species
Chemical activation
Glycerophospholipids
phorbol-12-myristate
Mutant Proteins
Hydrolysis
Fatty Acids
Degradation

Keywords

  • cPLA α
  • NF-κB
  • PKCδ
  • PMA
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A pathway involving protein kinase Cδ up-regulates cytosolic phospholipase A 2α in airway epithelium. / You, Hye Jin; Lee, Jee Won; Yoo, Yung Joon; Kim, Jae-Hong.

In: Biochemical and Biophysical Research Communications, Vol. 321, No. 3, 27.08.2004, p. 657-664.

Research output: Contribution to journalArticle

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