Ontogeny of [delta]-glutamyl transferase in the rat lung.
Oakes, Sean M., Yuji Takahashi, Mary C. Williams, and Martin Joyce
-Brady.
Pulmonary Center, Department of Medicine, Boston University School
of Medicine
APStracts 3:0215L, 1996.
GTis a key enzyme in the metabolism of glutathione and glutathione
-substituted molecules. The [delta]GT gene is expressed in two
epithelial cells of the adult lung; the bronchiolar Clara cell and
the alveolar type 2 cell. Since pulmonary glutathione metabolism may
be important in the perinatal period, we studied [delta]GT ontogeny
in the developing rat lung. In the late fetal and early postnatal
lung, [delta]GT mRNA was below detectable limits on northern blots.
Pulmonary [delta]GT protein and enzyme activity were present at low
levels after fetal day 18. [delta]GT protein appeared as a high
molecular weight band (>95 kD) with small amounts of enzymatically
active [delta]GT heterodimer. Between the second and third postnatal
weeks, pulmonary [delta]GT mRNA expression increased in association
with an increase in [delta]GT protein and enzyme activity which
reached adult lung levels. At this time [delta]GT protein appeared
predominantly in the heterodimeric form with small amounts of the
>95 kD protein. Immunocytochemistry revealed that in the fetal and
early postnatal lung [delta]GT was expressed only in the alveolar
type 2 cell, whereas the Clara cell became the major site of
[delta]GT mRNA and protein expression by 2-3 weeks and in the adult.
Type 2 cells isolated from the fetal lung express [delta]GT mRNA and
synthesize the >95 kD form of [delta]GT in excess of the
heterodimer. These studies demonstrate that the alveolar type 2 cell
is the only cell producing [delta]GT in the newborn lung and that it
synthesizes a form of [delta]GT which appears to differ from that
produced at a later time point by the Clara cell.
Received 15 July 1996; accepted in final form 4 November 1996.
APS Manuscript Number L219-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996