Regulation of cyclooxygenase and 12-lipoxygenase catalysis by phospholipid hydroperoxide glutathione peroxidase in A431 cells

Glutathione peroxidase 4 has a major role in protecting mitochondria from oxidative damage and maintaining oxidative phosphorylation complexes in gut epithelial cells

“…Overexpression of GPX4 in GPX4 þ / À mice lowered liver damage in cells treated with diquat, reduced apoptosis, and reduced activation of caspase-3 and cytochrome c release [19]. Third, GPx4 overexpression in cell culture models leads to altered eicosanoid metabolism [22,23] and a genetic polymorphism in the GPX4 gene (rs713041) is linked to differences in blood cell lipoxygenase metabolite levels [24]. In this regard, recent studies have indicated that decreased GPx4 activity leads to increased levels of oxidized peroxides derived from 15-OOH eicosatetraenoic acid as a result of 12/15 lipoxygenase activity [25], and this can lead to increased cell death [26].…”

Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia

“…Although all eight have peroxidase activity thought to protect the organism from oxidative damage, GPX4 is unique in that it alone is involved in arachidonate metabolism and eicosanoid biosynthesis 13 14. Of even greater pathogenic importance, GPX4 has broader substrate specificity than the other family members and, in addition to the reduction of small hydrophobic peroxides such as H 2 O 2, it reduces more complex substrates such as phospholipids, cholesterol, and cholesterol ester hydroperoxides, even those incorporated into membranes or lipoproteins (reviewed in Brigelius-Flohe and Maiorino15).…”

Inhibition of arachidonate metabolism in human epidermoid carcinoma A431 cells overexpressing phospholipid hydroperoxide glutathione peroxidase

“…The immunoblot analysis ( fig. We previously reported that the addition of 13-HPODE could stimulate lipid oxygenation in A431 cells [4]. In an intact cell assay in the absence of 13-HPODE ( fig.…”

“…Moreover, the purified inhibitor exhibited peroxidase activity using phosphatidylcholine hydroperoxides as a substrate [8]. Depletion of GSH in cells resulted in upregulation of the enzyme activities of cyclooxygenase and 12-1ipoxygenase, and treatment of cells with the antisense oligonucleotide for PHGPx triggered the activation of cyclooxygenase and 12-1ipoxygenase [4]. Depletion of GSH in cells resulted in upregulation of the enzyme activities of cyclooxygenase and 12-1ipoxygenase, and treatment of cells with the antisense oligonucleotide for PHGPx triggered the activation of cyclooxygenase and 12-1ipoxygenase [4].…”

“…Previous experiments [4] using GSH inhibitors and PHGPx antisense provided evidence indicating that PHGPx may play a functional role in arachidonate metabolism. To further confirm this notion, in the present study, we generated stable transfectants of overexpressing PHGPx.…”