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Ontogeny of c-glutamyltransferase in the rat lung

Oakes, S.M.; Takahashi, Y.; Williams, M.C.

American Journal of Physiology 272: 39-L744

1997


ISSN/ISBN: 0363-6143
Accession: 009929587

c-Glutamyltransferase (c-GT) is a key enzyme in the metabolism of glutathione and glutathione-substituted molecules. The c-GT gene is expressed in two epithelial cells of the adult lung, the bronchiolar Clara cell and the alveolar type II cell. Because pulmonary glutathione metabolism may be important in the perinatal period, we studied c-GT ontogeny in the developing rat lung. In the late fetal and early postnatal lung, c-GT mRNA was below detectable limits on Northern blots. Pulmonary c-GT protein and enzyme activity were present at low levels after fetal day 18. c-GT protein appeared as a high-molecular-mass band (>95 kDa), with small amounts of enzymatically active c-GT heterodimer. Between the 2nd and 3rd postnatal wk, pulmonary c-GT mRNA expression increased in association with an increase in c-GT protein and enzyme activity that reached adult lung levels. At this time, c-GT protein appeared predominantly in the heterodimeric form with small amounts of the >95-kDa protein. Immunocytochemistry revealed that, in the fetal and early postnatal lung, c-GT was expressed only in the alveolar type II cell, whereas the Clara cell became the major site of c-GT mRNA and protein expression by 2-3 wk and in the adult. Type II cells isolated from the fetal lung express c-GT mRNA and synthesize the >95-kDa form of c-GT in excess of the heterodimer. These studies demonstrate that the alveolar type II cell is the only cell producing c-GT in the newborn lung and that it synthesizes a form of c-GT that appears to differ from that produced at a later time point by the Clara cell. Reprinted by permission of the publisher.

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