Hydrogen peroxide-induced c-fos expression is mediated by arachidonic acid release

Role of protein kinase C

Rao Gadiparthi, Bernard Lassegue, Kathy K. Griendling, R. Wayne Alexander, Bradford C. Berk

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

We found previously that stimulation of c-fos and c-myc mRNA expression are early events in hydrogen peroxide-induced growth in rat aortic smooth muscle (RASM) cells. In the present study, we investigated the role of phospholipase A2 (PLA2 and protein kinase C (PKC) in mediating hydrogen peroxide-induced c-fos mRNA expression in RASM cells. Mepacrine and p-bromophenacylbromide, potent inhibitors of PLA2 activity, blocked hydrogen peroxide-induced c-fos mRNA expression. Arachldonic acid, a product of PLA2 activity, stimulated the expression of c-fos mRNA with a time course similar to that of hydrogen peroxide. PKC down-regulation attenuated both hydrogen peroxide and arachldonic acid-induced c-fos mRNA expression by 50%. Nordihydrogualaretic acid (a lipoxygenase-cytochrome P450 monooxygenase inhibitor) significantly inhibited both hydrogen peroxide and arachidonlc acid-induced c-fos mRNA expression, whereas indomethacin (a cydooxygenase inhibitor) had no effect. Together, these findings indicate that 1) hydrogen peroxide-induced c-fos mRNA expression is mediated by PLA2-dependent arachidonlc acid release, 2) both PKC-dependent and independent mechanisms are involved in hydrogen peroxide-induced expression of c-fos mRNA and 3) arachidonlc acid metabolism via the lipoxygenase-cytochrome P450 monooxygenase pathway appears to be required for hydrogen peroxide-induced expression of c-fos mRNA.

Original languageEnglish (US)
Pages (from-to)1259-1263
Number of pages5
JournalNucleic acids research
Volume21
Issue number5
DOIs
StatePublished - Mar 11 1993

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Arachidonic Acid
Protein Kinase C
Hydrogen Peroxide
Messenger RNA
Acids
Lipoxygenase
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Smooth Muscle Myocytes
Quinacrine
Phospholipases A2
Indomethacin
Down-Regulation
Growth

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Hydrogen peroxide-induced c-fos expression is mediated by arachidonic acid release : Role of protein kinase C. / Gadiparthi, Rao; Lassegue, Bernard; Griendling, Kathy K.; Alexander, R. Wayne; Berk, Bradford C.

In: Nucleic acids research, Vol. 21, No. 5, 11.03.1993, p. 1259-1263.

Research output: Contribution to journalArticle

Gadiparthi, Rao ; Lassegue, Bernard ; Griendling, Kathy K. ; Alexander, R. Wayne ; Berk, Bradford C. / Hydrogen peroxide-induced c-fos expression is mediated by arachidonic acid release : Role of protein kinase C. In: Nucleic acids research. 1993 ; Vol. 21, No. 5. pp. 1259-1263.
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abstract = "We found previously that stimulation of c-fos and c-myc mRNA expression are early events in hydrogen peroxide-induced growth in rat aortic smooth muscle (RASM) cells. In the present study, we investigated the role of phospholipase A2 (PLA2 and protein kinase C (PKC) in mediating hydrogen peroxide-induced c-fos mRNA expression in RASM cells. Mepacrine and p-bromophenacylbromide, potent inhibitors of PLA2 activity, blocked hydrogen peroxide-induced c-fos mRNA expression. Arachldonic acid, a product of PLA2 activity, stimulated the expression of c-fos mRNA with a time course similar to that of hydrogen peroxide. PKC down-regulation attenuated both hydrogen peroxide and arachldonic acid-induced c-fos mRNA expression by 50{\%}. Nordihydrogualaretic acid (a lipoxygenase-cytochrome P450 monooxygenase inhibitor) significantly inhibited both hydrogen peroxide and arachidonlc acid-induced c-fos mRNA expression, whereas indomethacin (a cydooxygenase inhibitor) had no effect. Together, these findings indicate that 1) hydrogen peroxide-induced c-fos mRNA expression is mediated by PLA2-dependent arachidonlc acid release, 2) both PKC-dependent and independent mechanisms are involved in hydrogen peroxide-induced expression of c-fos mRNA and 3) arachidonlc acid metabolism via the lipoxygenase-cytochrome P450 monooxygenase pathway appears to be required for hydrogen peroxide-induced expression of c-fos mRNA.",
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