AJP - Lung Cellular and Molecular Physiology, Vol 272, Issue 4 739-L744, Copyright © 1997 by American Physiological Society

ARTICLES

Ontogeny of gamma-glutamyltransferase in the rat lung

S. M. Oakes, Y. Takahashi, M. C. Williams and M. Joyce-Brady
Pulmonary Center, Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.

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

This article has been cited by other articles:

				J.-C. Jean, C. B. Rich, and M. Joyce-Brady Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L950 - L956. [Abstract] [Full Text] [PDF]

				J. C. Jean, Y. Liu, L. A. Brown, R. E. Marc, E. Klings, and M. Joyce-Brady gamma -Glutamyl transferase deficiency results in lung oxidant stress in normoxia Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L766 - L776. [Abstract] [Full Text] [PDF]

				J.-C. Jean, I. Eruchalu, Y. X. Cao, and M. Joyce-Brady DANCE in developing and injured lung Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L75 - L82. [Abstract] [Full Text] [PDF]

				J. C. Jean, C. O. Harding, S. M. Oakes, Q. Yu, P. K. Held, and M. Joyce-Brady {gamma}-Glutamyl transferase (GGT) deficiency in the GGTenu1 mouse results from a single point mutation that leads to a stop codon in the first coding exon of GGT mRNA Mutagenesis, January 1, 1999; 14(1): 31 - 36. [Abstract] [Full Text] [PDF]

				R.-M. Liu, M. M. Shi, C. Giulivi, and H. J. Forman Quinones increase gamma -glutamyl transpeptidase expression by multiple mechanisms in rat lung epithelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 1998; 274(3): L330 - L336. [Abstract] [Full Text] [PDF]