Skeletal Muscles Express the Xenobiotic-metabolizing Enzyme Arylamine N-acetyltransferaseFernando RodriguesLimaa,b, Racquel N. Coopera, Bertrand Goudeaua, Noureddine Atmanea, Anne-Marie Chamagnea, Gillian ButlerBrownea, Edith Simc, Patrick Vicarta,b, and Jean-Marie Dupreta,ba CNRS-UMR7000, Faculté de Médecine Pitié-Salpêtrière, Paris, France b UFR de Biochimie, Université Denis Diderot-Paris 7, Paris, France c Oxford University, Department of Pharmacology, Oxford, United Kingdom Correspondence to: Jean-Marie Dupret, UMR7000, Faculté de Médecine Pitié-Salpêtrière, 105 bd de l'Hôpital, 75013 Paris, France. E-mail: jmdupret@infobiogen.fr The human arylamine N-acetyltransferases (NATs) NAT1 and NAT2 are enzymes responsible for the acetylation of many arylamines and hydrazines, thereby playing an important role in both detoxification and activation of many drugs and carcinogens. Both enzymes show polymorphisms but exhibit key differences in substrate selectivity and tissue expression. In the present study, reverse transcriptase-PCR, Western blotting, and immunohistochemistry were used to investigate the expression of the NATs in human skeletal muscle. Despite the presence of its mRNA, NAT2 enzyme level was below the limit of detection. In contrast, both NAT1 mRNA and enzyme were readily detected in fetal, newborn, and adult muscles. In addition, punctate cytoplasmic and perinuclear NAT1 immunostaining was observed in all tissue sections, the staining being more intense in the fetal tissue. High expression of NAT1 enzyme in fetal muscle was also suggested by Western blotting. Because skeletal muscle accounts for a large proportion of body mass, muscle NAT1 expression may contribute significantly to the total activity in the body. These results further support the involvement of skeletal muscle in the metabolism of xenobiotics. (J Histochem Cytochem 51:789796, 2003) Key Words: NATs, xenobiotics, human skeletal muscle, RT-PCR, immunohistochemistry, Western blotting
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