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In vivo measurement of aldehyde dehydrogenase‐2 activity in rat liver ethanol model using dynamic MRSI of hyperpolarized [1‐ 13 C]pyruvate
Author(s) -
Josan Sonal,
Xu Tao,
Yen YiFen,
Hurd Ralph,
Ferreira Julio,
Chen CheHong,
MochlyRosen Daria,
Pfefferbaum Adolf,
Mayer Dirk,
Spielman Daniel
Publication year - 2013
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.2897
Subject(s) - in vivo , chemistry , acetaldehyde , aldh2 , aldehyde dehydrogenase , lactate dehydrogenase , nicotinamide adenine dinucleotide , pyruvic acid , ethanol , biochemistry , nad+ kinase , cofactor , enzyme , biology , microbiology and biotechnology
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 T 1 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). Copyright © 2012 John Wiley & Sons, Ltd.