Document Detail


In vivo measurement of aldehyde dehydrogenase-2 activity in rat liver ethanol model using dynamic MRSI of hyperpolarized [1-(13) C]pyruvate.
MedLine Citation:
PMID:  23225495     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To date, measurements of the activity of aldehyde dehydrogenase-2 (ALDH2), a critical mitochondrial enzyme for the elimination of certain cytotoxic aldehydes in the body and a promising target for drug development, have been largely limited to in vitro methods. Recent advancements in MRS of hyperpolarized (13) C-labeled substrates have provided a method to detect and image in vivo metabolic pathways with signal-to-noise ratio gains greater than 10 000-fold over conventional MRS techniques. However aldehydes, because of their toxicity and short T1 relaxation times, are generally poor targets for such (13) C-labeled studies. In this work, we show that dynamic MRSI of hyperpolarized [1-(13) C]pyruvate and its conversion to [1-(13) C]lactate can provide an indirect in vivo measurement of ALDH2 activity via the concentration of NADH (nicotinamide adenine dinucleotide, reduced form), a co-factor common to both the reduction of pyruvate to lactate and the oxidation of acetaldehyde to acetate. Results from a rat liver ethanol model (n = 9) show that changes in (13) C-lactate labeling following the bolus injection of hyperpolarized pyruvate are highly correlated with changes in ALDH2 activity (R(2) = 0.76).
Authors:
Sonal Josan; Tao Xu; Yi-Fen Yen; Ralph Hurd; Julio Ferreira; Che-Hong Chen; Daria Mochly-Rosen; Adolf Pfefferbaum; Dirk Mayer; Daniel Spielman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-06
Journal Detail:
Title:  NMR in biomedicine     Volume:  26     ISSN:  1099-1492     ISO Abbreviation:  NMR Biomed     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-23     Completed Date:  2013-11-08     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8915233     Medline TA:  NMR Biomed     Country:  England    
Other Details:
Languages:  eng     Pagination:  607-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Dehydrogenase / antagonists & inhibitors,  metabolism*
Animals
Carbon Isotopes / diagnostic use
Disulfiram / pharmacology
Liver / enzymology*
Magnetic Resonance Spectroscopy / methods*
Male
Mitochondrial Proteins / antagonists & inhibitors,  metabolism*
Pyruvic Acid / metabolism*
Rats
Rats, Wistar
Grant Support
ID/Acronym/Agency:
AA018681/AA/NIAAA NIH HHS; AA05965/AA/NIAAA NIH HHS; AA13521/AA/NIAAA NIH HHS; EB009070/EB/NIBIB NIH HHS; P41 EB015891/EB/NIBIB NIH HHS; P41 EB015891L/EB/NIBIB NIH HHS; R01 AA005965/AA/NIAAA NIH HHS; R01 AA018681/AA/NIAAA NIH HHS; R01 EB009070/EB/NIBIB NIH HHS; U01 AA013521/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 0/Mitochondrial Proteins; 8558G7RUTR/Pyruvic Acid; EC 1.2.1.3/Aldehyde Dehydrogenase; EC 1.2.1.3/Aldh2 protein, rat; TR3MLJ1UAI/Disulfiram
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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