OxyFile #214

Role of hydroperoxyeicosatetraenoic acids in oxidative 
stress-induced activating protein 1 (AP-1) activity.

Author:  Rao GN; Glasgow WC; Eling TE; Runge MS

Source:  J Biol Chem 1996 Nov 1; 271(44):27760-4


We have previously reported that hydrogen peroxide, an 
active oxygen species and a cellular oxidant, induces c-Fos 
and c-Jun mRNA expression and DNA synthesis in vascular 
smooth muscle cells and that these events require arachidonic 
acid release and metabolism through the lipoxygenase pathway. 
Here we have identified the eicosanoids that mediate the 
hydrogen peroxide-induced growth-related events in these 
cells. Hydrogen peroxide stimulated the production of 12- 
and 15-hydroperoxyeicosatetraenoic acids in vascular smooth 
muscle cells. Both 12- and 15-hydroperoxyeicosatetraenoic 
acids induced the expression of c-Fos and c-Jun protein 
and increased activating protein 1 (AP-1) activity, as 
measured by AP-1-DNA binding and AP-1-dependent human collagenase 
promoter-driven chloramphenicol acetyltransferase reporter 
gene transcription. Hydrogen peroxide and arachidonic acid 
also induced the expression of c-Fos and c-Jun protein 
and AP-1 activity. Nordihydroguaiaretic acid, an inhibitor 
of the lipoxygenase pathway, significantly inhibited both 
hydrogen peroxide and arachidonic acid-stimulated c-Fos 
and c-Jun protein expression and AP-1 activity. Together, 
these findings suggest that hydrogen peroxide induces the 
production of eicosanoids and that the eicosanoids are 
potential mediators of the oxidative stress-stimulated 
growth-related events in vascular smooth muscle cells.