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Journal of Nutrition, doi:10.3945/jn.108.089482
Vol. 138, No. 12, 2328-2336, December 2008

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© 2008 American Society for Nutrition


Biochemical, Molecular, and Genetic Mechanisms

Redox Regulation of Protein Tyrosine Phosphatase 1B by Manipulation of Dietary Selenium Affects the Triglyceride Concentration in Rat Liver1,2

Andreas S. Mueller3,4,*, Sandra D. Klomann5, Nicole M. Wolf5, Sandra Schneider6, Rupert Schmidt6, Julia Spielmann3, Gabriele Stangl3, Klaus Eder3 and Josef Pallauf5

3 Institute of Agricultural and Nutritional Sciences, and 4 Preventive Nutrition Group, Martin Luther University Halle Wittenberg, D-06120 Halle/Saale, Germany, 5 Interdisciplinary Research Centre, Department of Animal Nutrition and Nutritional Physiology, and 6 Biotechnology Center, Justus Liebig University Giessen, D-35392 Giessen, Germany

Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme in the counter-regulation of insulin signaling and in the stimulation of fatty acid synthesis. Selenium (Se), via the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), is involved in the removal of H2O2 and organic peroxides, which are critical compounds in the modulation of PTP1B activity via glutathionylation. Our study with growing rats investigated how the manipulation of dietary Se concentration influences the regulation of PTP1B and lipogenic effects mediated by PTP1B. Weanling albino rats were divided into 3 groups of 10. The negative control group (NC) was fed a Se-deficient diet for 8 wk. Rats in groups Se75 and Se150 received diets supplemented with 75 or 150 µg Se/kg. Se supplementation of the rats strongly influenced expression and activity of the selenoenzymes cytosolic GPx, plasma GPx, phospholipidhydroperoxide GPx, and cytosolic TrxR, and liver PTP1B. Liver PTP1B activity was significantly higher in groups Se75 and Se150 than in the NC group and this was attributed to a lowered inhibition of the enzyme by glutathionylation. The increased liver PTP1B activity in groups Se75 and Se150 resulted in 1.1- and 1.4-fold higher liver triglyceride concentrations than in the NC rats. The upregulation of the sterol regulatory element binding protein-1c and of fatty acid synthase, 2 PTP1B targets, provided a possible explanation for the lipogenic effect of PTP1B due to the manipulation of dietary Se. We therefore conclude that redox-regulated proteins, such as PTP1B, represent important interfaces between dietary antioxidants such as Se and the regulation of metabolic processes.


* To whom correspondence should be addressed. Email: andreas.mueller{at}landw.uni-halle.de.

Manuscript received 10 March 2008. Initial review completed 30 April 2008. Revision accepted 2 October 2008.







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