Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/28/2010
Publication Date: 4/24/2010
Publication URL: http://www.fasebj;org
Citation: Jackson, M.I., Combs, G.F. 2010. Impaired Homocysteine Transmethylation and Protein-Methyltransferase Activity Reduce Expression of Selenoprotein P: Implications for Obesity and Metabolic Syndrome. Journal of Federation of American Societies for Experimental Biology. 24:lb280 Interpretive Summary:
Technical Abstract: Obesity causes Metabolic Syndrome and Type-II Diabetes, disrupting hepatic function, methionine (Met)/homocysteine (Hcy) transmethylation and methyltransferase (PRMT) activities. Selenoprotein P (SEPP1), exported from the liver, is the predominate form of plasma selenium (Se) and the physiological Se delivery mechanism to extrahepatic tissues. SEPP1 expression is effected by transfactors subject to post-translational methylation and depends upon methylation of tRNA and methylation status of gene promoter regions. Se is capable of anti-carcinogenic activity: we found plasma Se status to vary with body mass index. Therefore, we sought to know whether Se metabolism is affected by obesity and, specifically, whether methylation capacity dictates the expression of SEPP1. In order to test that hypothesis, we treated HepG2 cells with mechanistically distinct inhibitors of S-adenosyl homocysteine hydrolase (AHCY), or PRMT. We found incubation with these agents to decrease the appearance of SEPP1 in HepG2 cell-conditioned media, which served as a model for plasma, and that the decrease in SEPP1 was not due to sequestration within cells. Thus, deficiencies in the Met/Hcy cycle or in the activity of methyltransferases, can reduce the expression of SEPP1. This suggests that it may be useful to determine whether obesity-impaired methylation result in decreased plasma levels of SEPP1 in animals and humans Se.