Cell Death Caused by Selenium Deficiency and Protective Effect of Antioxidants

Abstract

Selenium is an essential trace element and it is well known that selenium is necessary for cell culture. However, the mechanism underlying the role of selenium in cellular proliferation and survival is still unknown. The present study using Jurkat cells showed that selenium deficiency in a serum-free medium decreased the selenium-dependent enzyme activity (glutathione peroxidases and thioredoxin reductase) within cells and cell viability. To understand the mechanism of this effect of selenium, we examined the effect of other antioxidants, which act by different mechanisms. Vitamin E, a lipidsoluble radical-scavenging antioxidant, completely blocked selenium deficiency-induced cell death, although ␣-tocopherol (biologically the most active form of vitamin E) could not preserve selenium-dependent enzyme activity. Other antioxidants, such as different isoforms and derivatives of vitamin E, BO-653 and deferoxamine mesylate, also exerted an inhibitory effect. However, the water-soluble antioxidants, such as ascorbic acid, N-acetyl cysteine, and glutathione, displayed no such effect. Dichlorodihydrofluorescein (DCF) assay revealed that cellular reactive oxygen species (ROS) increased before cell death, and sodium selenite and ␣-tocopherol inhibited ROS increase in a dose-dependent manner. The generation of lipid hydroperoxides was observed by fluorescence probe diphenyl-1-pyrenylphosphine (DPPP) and HPLC chemiluminescence only in selenium-deficient cells. These results suggest that the ROS, especially lipid hydroperoxides, are involved in the cell death caused by selenium deficiency and that selenium and vitamin E cooperate in the defense against oxidative stress upon cells by detoxifying and inhibiting the formation of lipid hydroperoxides.

Preparation of keratinocyte culture medium for the clinical applications of regenerative medicine

“…However, the recombinant form of human transferrin remains to be developed, and purified human or bovine proteins were used in this study. Additionally, selenium is also believed to be an essential trace element for cell culture under serum-free conditions (McKeehan et al, 1976), probably due to its protective antioxidant effects (Saito et al, 2003). However, although the modified KCM was without transferrin or selenium, the efficiency in promoting the successful fabrication of canine oral mucosal epithelial cell sheets was similar to that of the control KCM formulation.…”

Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice

“…Selenium modulates p53 activity by a redox mechanism through the redox factor Ref1 (43), or by a phosphorylation mechanism (44), and inhibits NF-nB and p38 signaling pathways (45,46). On the other hand, it was recently shown that selenium deficiency caused cell death due to accumulation of reactive oxygen species, especially lipid peroxides (47). This effect probably explains the results of Novoselov et al showing antihepatocarcinogenic effect in a transgenic mouse model both at high levels of selenium and at selenium deficiency but not at intermediate selenium levels (12).…”

The protective efficacy of vitamins (C and E), selenium and silymarin supplements against alcohol toxicity

“…Marino et al (2004) showed that vitamin E protects against alcohol induced oxidative stress. The presence of selenium in combination with vitamin E enhanced its activity in removing free radicals and prevented their formation (Saito et al, 2003).…”