Document Detail


Penultimate selenocysteine residue replaced by cysteine in thioredoxin reductase from selenium-deficient rat liver.
MedLine Citation:
PMID:  19351701     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Selenium is an essential micronutrient for humans and animals, and its deficiency can predispose to the development of pathological conditions. This study evaluates the effect of selenium deficiency on the thioredoxin system, consisting of NADPH, selenoprotein thioredoxin reductase (TrxR), and thioredoxin (Trx); and the glutathione system, including NADPH, glutathione reductase, glutathione, and glutaredoxin coupled with selenoprotein glutathione peroxidase (GPx). We particularly investigate whether inactive truncated TrxR is present under selenium-starvation conditions due to reading of the UGA codon as stop. Feeding rats a selenium-deficient diet resulted in a large decrease in activity of TrxR and GPx in rat liver but not in the levels of Trx1 and Grx1. However, selenium deficiency induced mitochondrial Grx2 10-fold and markedly changed the expression of some flavoproteins that are involved in the cellular folate, glucose, and lipid metabolism. Liver TrxR mRNA was nearly unchanged, but no truncated enzyme was found. Instead, a low-activity form of TrxR with a cysteine substituted for the penultimate selenocysteine in the C-terminal active site was identified in selenium-deficient rat liver. These results show a novel mechanism for decoding the UGA stop codon, inserting cysteine to make a full-length enzyme that may be required for selenium assimilation.
Authors:
Jun Lu; Liangwei Zhong; Maria Elisabet Lönn; Raymond F Burk; Kristina E Hill; Arne Holmgren
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-04-07
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  23     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-31     Completed Date:  2009-08-18     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2394-402     Citation Subset:  IM    
Affiliation:
Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-171 77 Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Codon, Terminator / genetics
Cysteine / chemistry
Feedback, Physiological
Glutaredoxins / genetics,  metabolism
Liver / enzymology*
Male
Models, Biological
RNA, Messenger / genetics,  metabolism
Rats
Rats, Sprague-Dawley
Selenium / deficiency*
Selenocysteine / chemistry*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Thioredoxin Reductase 1 / chemistry*,  genetics,  metabolism
Thioredoxins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
ES02497/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Codon, Terminator; 0/Glrx1 protein, rat; 0/Glutaredoxins; 0/RNA, Messenger; 0/Txn1 protein, rat; 10236-58-5/Selenocysteine; 52-90-4/Cysteine; 52500-60-4/Thioredoxins; 7782-49-2/Selenium; EC 1.8.1.9/Thioredoxin Reductase 1; EC 1.8.1.9/Txnrd1 protein, rat
Comments/Corrections

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