Role of Hydroperoxyeicosatetraenoic Acids in Oxidative Stress-induced Activating Protein 1 (AP-1) Activity

Gadiparthi N. Rao, Wayne C. Glasgow, Thomas E. Eling, Marschall S. Runge
1996 Journal of Biological Chemistry  
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
more » ... 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 stressstimulated growth-related events in vascular smooth muscle cells. Active oxygen (AO) 1 species such as superoxide anion, hydrogen peroxide, and hydroxyl radicals are constantly formed in all aerobic cells as a result of mitochondrial electron transport and several enzymatic reactions such as xanthine oxidase, NADH/NADPH oxidase, monooxygenases, and cyclooxygenases (1-3). These AO species damage DNA, lipids, and protein (1-3). However, several cellular antioxidant defenses such as superoxide dismutase, catalase, glutathione peroxidase, vitamin C, and vitamin E protect cells from such toxins (1-3). The production of AO species in any given cell varies, depending on
doi:10.1074/jbc.271.44.27760 pmid:8910370 fatcat:z2iot7x7yfdgjbztlyywkxhqyu