The Protective Role of Glutathione Peroxidase in Apoptosis Induced by Reactive Oxygen Species

Abstract

Selenium-dependent glutathione peroxidase (GPx) plays a protective role in oxidative stress-induced apoptosis. In this study, we demonstrated that MDBK cells, a bovine renal epithelial cell line, exhibited internucleosomal DNA fragmentation characteristic of apoptotic cell death under selenium-deficient conditions with lower doses of hydrogen peroxide (H2O2) than under selenium-supplemented ones. This was due to a decreased amount of GPx in the cells under selenium-deficient conditions, because other antioxidative enzyme activities were not affected by the selenium supplementation. Cumene hydroperoxide also induced DNA fragmentation in selenium-deficient cells but no ladder formation was observed. Flow cytometric analysis showed that selenium-deficient cells were less capable of scavenging intracellular peroxides after exposure to exogenous H2O2 than selenium-supplemented ones. In contrast, there was no difference in viability between selenium-supplemented and non-supplemented cells in cell survival after exposure to menadione, which activates the electron transport system and increases intracellular superoxide radicals. Clofibrate, a peroxisomal proliferator and an inducer of catalase (CAT), partially protected both Se-deficient and Se-supplemented cells from exogenous H202. We concluded that selenium-deficient cells were more easily brought to apoptotic cell death by peroxides, but not by superoxide radicals, than selenium-supplemented ones and that CAT could compensate for the depletion of GPx to a certain degree by scavenging H2O2.

Apoptosis and glutathione: beyond an antioxidant

“…GPX1 whose preferred substrate is hydrogen peroxide is the most abundant isoform found in the cytoplasm of nearly all mammalian tissues whereas GPX2 is an intestinal and extracellular enzyme. 82 GPX1 and GPX2 have been reported to protect against apoptosis induced by oxidative stress 83,84 ischemia/reperfusion injury 85 and doxorubicin 86 and to reduce pro-apoptotic Bax expression. 87 GPX4 (also known as phospholipid hydroperoxide glutathione peroxidase, PHGPX) overexpression has been reported to protect against oxidative stress-induced apoptosis.…”

Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

“…However, since in cultured hepatocytes the reexpression of subunit P1 is inhibited by dimethyl sulfoxide (38), this suggests a possible correlation between the expression and IL-1 induction of subunit P1 and its high glutathione peroxidase activity. Moreover, it was demonstrated that in cells treated with IL-1 for 24 h, there was a marked increase in the intracellular content of hydroperoxides (40). As a result of an increased exposure to reactive oxygen species after IL-1 treatment, cultured hepatocytes could respond by increasing their glutathione peroxidase activity.…”

Vascular Apoptosis and Involution in Gliomas Precede Neovascularization: A Novel Concept for Glioma Growth and Angiogenesis

“…Apoptotic death of vascular cells results from transduction of death signals triggered by various exogenous stimuli including (a) cytokines, eg, tumor necrosis factor-␣ (TNF␣) (Geng et al, 1996;Robaye et al, 1991); (b) Fas/Fas ligand signaling (Kagi et al, 1994;Nagata, 1997); (c) loss of extracellular matrix (ECM) contacts (anoikis) (Bates et al, 1994;Frisch and Francis, 1994;Re et al, 1994;Ruoslahti and Reed, 1994); (d) hypoxia (Stempien-Otero et al, 1999) and reactive oxygen species (Kayanoki et al, 1996;Li et al, 1997); and (e) withdrawal of a trophic factor, eg, bFGF (Fox and Shanley, 1996) or VEGF (Benjamin et al, 1999;Benjamin and Keshet, 1997). Cytokines released by glioma cells (Zagzag, 1995), eg, TNF-␣ (Geng et al, 1998;Robaye et al, 1991) and TGF-␤ (Pollman et al, 1996), are able to cause apoptosis of endothelial and smooth muscle cells.…”