Studies on the inhibition of protein synthesis by selenodiglutathione

Vernie, L.N.; Collard, John G.; Eker, A.P.M.; Wildt, A. De; Wilders, I.T.

doi:10.1042/bj1800213

Cited by 44 publications

(10 citation statements)

References 17 publications

(21 reference statements)

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“…In addition to the known inhibition of specific isolated enzymes (18)(19)(20)(21)(22) by selenite and RS-Se-SR types of thiol adducts, inhibitory effects that can result from inactivation of essential thiol groups of transcription factors such as AP-1 (23) and NF-B, which control many cellular processes, may be greatly amplified and become global in nature. More detailed study of this type of regulation of cellular activity by selenium compounds may help to explain the well known but poorly understood toxicity of selenium.…”

Section: Discussionmentioning

confidence: 99%

“…In the absence of oxygen, growth of selenium-requiring anerobic bacteria usually is inhibited when selenite levels are increased 10-fold above the required 0.5-to 1-M levels. Several enzymes that contain essential reactive sulfhydryl groups have been shown to be especially sensitive to selenite treatment (18)(19)(20)(21)(22). Inhibition due to formation of a selenotrisulfide type of adduct was established as the mechanism of selenite action in the case of rat brain prostaglandin D synthase (19), and this inhibition was reversed by an excess of DTT.…”

mentioning

confidence: 99%

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Inhibition of NF-κB DNA binding and nitric oxide induction in human T cells and lung adenocarcinoma cells by selenite treatment

Kim

Stadtman

1997

Proc. Natl. Acad. Sci. U.S.A.

150

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NF-B is a major transcription factor consisting of 50(p50)-and 65(p65)-kDa proteins that controls the expression of various genes, among which are those encoding cytokines, cell adhesion molecules, and inducible NO synthase (iNOS). After initial activation of NF-B, which involves release and proteolysis of a bound inhibitor, essential cysteine residues are maintained in the active reduced state through the action of thioredoxin and thioredoxin reductase. In the present study, activation of NF-B in human T cells and lung adenocarcinoma cells was induced by recombinant human tumor necrosis factor ␣ or bacterial lipopolysaccharide. After lipopolysaccharide activation, nuclear extracts were treated with increasing concentrations of selenite, and the effects on DNA-binding activity of NF-B were examined. Binding of NF-B to nuclear responsive elements was decreased progressively by increasing selenite levels and, at 7 M selenite, DNA-binding activity was completely inhibited. Selenite inhibition was reversed by addition of a dithiol, DTT. Proportional inhibition of iNOS activity as measured by decreased NO products in the medium (NO 2 ؊ and NO 3 ؊ ) resulted from selenite addition to cell suspensions. This loss of iNOS activity was due to decreased synthesis of NO synthase protein. Selenium at low essential levels (nM) is required for synthesis of redox active selenoenzymes such as glutathione peroxidases and thioredoxin reductase, but in higher toxic levels (>5-10 M) selenite can react with essential thiol groups on enzymes to form RS-Se-SR adducts with resultant inhibition of enzyme activity. Inhibition of NF-B activity by selenite is presumed to be the result of adduct formation with the essential thiols of this transcription factor.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of NF-κB DNA binding and nitric oxide induction in human T cells and lung adenocarcinoma cells by selenite treatment

Kim

Stadtman

1997

Proc. Natl. Acad. Sci. U.S.A.

150

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“…These effects might be related to the recently demonstrated inhibition of protein synthesis by selenodiglutathione in mammalian cells, bacteria and in cell-free in vitro systems (Vernie et al, 1974(Vernie et al, , 1979. This compound also inhibits growth of a lymphoid tumor (L1210) in mice (Vernie et al, 1981) when administered intraperitoneally.…”

Section: Discussionmentioning

confidence: 97%

Effect of selenium on the induction of breast fibroadenomas by adenovirus type 9 and 1,2‐dimethylhydrazine‐induced bowel carcinogenesis in rats

Ankerst

Sjögren

1982

Intl Journal of Cancer

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Selenium in its organic and inorganic forms has been shown to inhibit the development of chemically induced, spontaneous and transplanted tumors. The present investigation was performed to study the effect of selenium (4 micrograms per ml of drinking water) on tumorigenesis of adenovirus-type-9-induced breast fibroadenomas and on 1,2-dimethylhydrazine-induced bowel carcinogenesis in WF rats. It was found that identical treatment with Se under identical conditions and with no obvious toxic effects on the rats (1) resulted in inhibition of DMH-induced large-bowel carcinogenesis; (2) facilitated induction of small-bowel cancer by the same carcinogen in the same animals, and (3) greatly facilitated induction of breast fibroadenoma by adenovirus type 9 in the same strain of rats. The effect of Se treatment on DMH-induced large-bowel carcinogenesis confirms previous findings and proves that the opposite effect on fibroadenoma development is not due to differences in e.g. effective dose, animal strains or condition of the animals. It is not yet clear through which mechanisms Se exerts these effects.

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“…Inhibition of DNA synthesis occurs prior to inhibition of general protein synthesis. However, in one experiment, inhibition of cell growth was accompanied by inhibition of protein syn thesis under conditions where DNA and RNA synthesis was not altered [63,64]. The inhibition of protein synthesis was corre lated with inhibition of elongation factor 2 [48,64] but not eukaryotic initiation factor 2 [46].…”

Section: Possible Mechanisms Of Selenium Actionmentioning

confidence: 97%