uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Binding of tellurium to hepatocellular selenoproteins during incubationwith inorganic tellurite: consequences for the activity ofselenium-dependent glutathione peroxidase
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (BMS)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (BMS)
Show others and affiliations
1999 (English)In: International Journal of Biochemistry and Cell Biology, ISSN 1357-2725, Vol. 31, no 2, 291-301 p.Article in journal (Refereed) Published
Abstract [en]

The metallic group XVIa elements selenium and tellurium possess remarkably similar chemical properties. However, unlike selenium, tellurium is not an essential micronutrient and, indeed, induces both acute and chronic toxicity in a variety of species. Despite this, very little is known of the molecular mechanisms of toxicity of tellurium, particularly with respect to potential chemical interactions with selenium-containing components in the cell. In this work we describe a novel interaction of inorganic tellurite with hepatocellular selenoproteins, particularly with selenium-dependent glutathione peroxidase. The accumulation of (121Te)-tellurite into cultured primary rat liver hepatocytes was shown to be much more rapid than that of (75Se)-selenite on a molar basis. Neither the uptake of (121Te)-tellurite nor of (75Se)-selenite was affected by a large molar excess of the unlabelled counterpart, respectively. Interestingly, separation of the hepatocellular proteins on continuous pH denaturing gels demonstrated clear binding of radiolabelled tellurium to a number of protein bands, including one at 23 and one at 58 kDa, which corresponded to proteins readily labelled in cells treated with (75Se)-selenite. The binding of (121Te) to these proteins was insensitive to reduction with mercaptoethanol and not affected by pre-treatment of the cells with cycloheximide. When purified selenium-dependent glutathione peroxidase was treated directly with (121Te)-tellurite, the protein became labelled in an analogous manner to that achieved in intact cells. This was not affected by coincubation of the enzyme with (121Te)-tellurite and one or both of its substrates. Additionally, incubation of the peroxidase with tellurite effectively inhibited its ability to catalyse glutathione-dependent reduction of hydrogen peroxide. These data suggest that inorganic tellurite delivers tellurium to the intracellular milieu in a form capable of binding to some intracellular selenoproteins and at least in the case of glutathione peroxidase, cause inhibition of catalytic activity. The nature of the binding seems not to be due to the insertion of tellurocysteine into the protein and the insensitivity to reductive cleavage with mercaptoethanol seems to preclude the formation of stable telluro-selenides in the proteins. These data may offer alternative explanations for the established toxicity of tellurium via disruption of selenoprotein function, particularly by the induction of intracellular oxidative stress by the inhibition of Se-dependent glutathione peroxidase.

Place, publisher, year, edition, pages
1999. Vol. 31, no 2, 291-301 p.
Keyword [en]
Tellurite, Hepatocytes, Selenoprotein, Glutathione peroxidase
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-57122DOI: 10.1016/S1357-2725(98)00113-7PubMedID: 10216961OAI: oai:DiVA.org:uu-57122DiVA: diva2:85031
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2014-03-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Tolmachev, Vladimir
By organisation
Department of Oncology, Radiology and Clinical Immunology
In the same journal
International Journal of Biochemistry and Cell Biology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 236 hits
ReferencesLink to record
Permanent link

Direct link