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Arylamine N-acetyltransferase 2 Expression in the Developing Heart

Larissa Wakefield, Valerie Cornish, Fiona Broackes-Carter and Edith Sim

Department of Pharmacology, University of Oxford, Oxford, UK

Correspondence to: Prof. Edith Sim, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. E-mail: edith.sim{at}pharm.ox.ac.uk

Murine arylamine N-acetyltransferase 2 (NAT2) is expressed in the developing heart and in the neural tube at the time of closure. Classically described as a xenobiotic metabolizing enzyme, there is increasing evidence for a distinct biological role for murine NAT2. We have characterized the expression of arylamine N-acetyltransferase 2 during cardiogenesis, mapping its expression in vivo, using a lacZ insertion deletion, and also in vitro, by measuring NAT2 enzyme activity. These findings show that cardiac Nat2 expression is both temporally and spatially regulated during development. In neonatal mice, cardiac Nat2 expression is most extensive in the central fibrous body and is evident in the atrioventricular valves and the valves of the great vessels. Whereas Nat2 expression is not detected in ventricular myocardial cells, Nat2 is strongly expressed in scattered cells in the region of the sinus node, the epicardium of the right atrial appendage, and in the pulmonary artery. Expression of active NAT2 protein is maximal when the developing heart attains the adult circulation pattern and moves from metabolizing glucose to fatty acids. NAT2 acetylating activity in cardiac tissue from Nat2^–/– and Nat2^+/– mice indicates a lack of compensating acetylating activity either from other acetylating enzymes or by NAT2 encoded by the wild-type Nat2 allele in Nat2^+/– heterozygotes. The temporal and spatial control of murine Nat2 expression points to an endogenous role distinct from xenobiotic metabolism and indicates that Nat2 expression may be useful as a marker in cardiac development.

(J Histochem Cytochem 53:583–592, 2005)

Key Words: arylamine N-acetyltransferase/ NAT • xenobiotic • autonomic nervous system • acetyl coenzyme A • knockout mouse

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