Hydrogen peroxide stimulates transcription of c-jun in vascular smooth muscle cells

Role of arachidonic acid

Rao Gadiparthi, B. Lassegue, K. K. Griendling, R. W. Alexander

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

We reported previously that hydrogen peroxide induces DNA synthesis in rat aortic smooth muscle (RASM) cells. In the present paper we studied the mechanism by which hydrogen peroxide induces c-jun mRNA, an early response gene whose activation is required for mitogen-stimulated cell growth. Hydrogen peroxide induced c-jun mRNA in growth-arrested RASM cells in a time dependent manner. This stimulation was significantly inhibited by mepacrine, a phospholipase A2 (PLA2) inhibitor. Arachidonic acid, a PLA2 product, also increased c-jun mRNA with a time course similar to that of hydrogen peroxide. The increases in c-jun mRNA induced by hydrogen peroxide and arachidonic acid were significantly reduced (55%) by down-regulation of protein kinase C with a phorbol ester. Furthermore, the effect of hydrogen peroxide on c-jun mRNA was also reduced by NDGA, an inhibitor of the lipoxygenase-cytochrome P450 monooxygenase system, suggesting that metabolism of arachidonic acid through this pathway is required for the induction of c-jun mRNA by oxidants. Both hydrogen peroxide and arachidonic acid significantly increased c-jun transcription as demonstrated by nuclear run-on assays. Together these observations suggest that: (1) the induction of c-jun mRNA by hydrogen peroxide is mediated by PLA2-dependent arachidonic acid release and metabolism through the lipoxygenase-cytochrome P450 mono-oxygenase system; (2) PKC appears to be involved in this signaling pathway and (3) the induction of c-jun mRNA by hydrogen peroxide in RASM cells is due to increased transcription.

Original languageEnglish (US)
Pages (from-to)2759-2764
Number of pages6
JournalOncogene
Volume8
Issue number10
StatePublished - 1993
Externally publishedYes

Fingerprint

Vascular Smooth Muscle
Arachidonic Acid
Hydrogen Peroxide
Smooth Muscle Myocytes
Messenger RNA
Phospholipases A2
Cytochrome P-450 Enzyme System
Quinacrine
Lipoxygenase Inhibitors
Oxygenases
Lipoxygenase
Phorbol Esters
Growth
Mixed Function Oxygenases
Mitogens
Oxidants
Protein Kinase C
Transcriptional Activation
Down-Regulation
DNA

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Hydrogen peroxide stimulates transcription of c-jun in vascular smooth muscle cells : Role of arachidonic acid. / Gadiparthi, Rao; Lassegue, B.; Griendling, K. K.; Alexander, R. W.

In: Oncogene, Vol. 8, No. 10, 1993, p. 2759-2764.

Research output: Contribution to journalArticle

Gadiparthi, R, Lassegue, B, Griendling, KK & Alexander, RW 1993, 'Hydrogen peroxide stimulates transcription of c-jun in vascular smooth muscle cells: Role of arachidonic acid', Oncogene, vol. 8, no. 10, pp. 2759-2764.
Gadiparthi, Rao ; Lassegue, B. ; Griendling, K. K. ; Alexander, R. W. / Hydrogen peroxide stimulates transcription of c-jun in vascular smooth muscle cells : Role of arachidonic acid. In: Oncogene. 1993 ; Vol. 8, No. 10. pp. 2759-2764.
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