Developmental expression of the pulmonary cytochrome p450
monooxygenase system during clara cell differentiation in rats.
Ji, Chun-Mei, Wellington V. Cardoso, Assefa Gebremichael, Richard M.
Philpot, Alan R. Buckpitt, Charles G. Plopper, and Kent E. Pinkerton.
Department of Anatomy, Physiology and Cell Biology (C.M.J., A.G.,
C.G.P., K.E.P.) and Department of Molecular Biosciences (A.R.B.),
School of Veterinary Medicine, University of California, Davis, CA
95616, Pulmonary Center (W.V.C.), Boston University School of
Medicine, Boston, MA 02118 and Laboratory of Cellular and Molecular
Pharmacology (R.M.P.), National Institute of Environmental Health
Sciences, Research Triangle Park, NC 27709.
APStracts 2:0087L, 1995.
Because a number of studies suggest that the developmental expression
of cytochrome P450s (CYP) in Clara cells is species-specific, this
study was designed to compare the developmental patterns of CYP2B and
NADPH reductase protein expression and CYP2B activity with the time
course of smooth endoplasmic reticulum (SER) formation in Clara cells
of rat lung. Pulmonary CYP2B activity measured as pentoxyresorufin O
-dealkylation in lung homogenates was not detectable before 7 days
postnatal age (DPN), but was at adult levels at 50 DPN. In Clara
cells, CYP2B and NADPH reductase were detected immunohistochemically
at 4 DPN and at adult levels at 10 DPN. The volume density of SER in
Clara cells of terminal bronchioles measured morphometrically
increased significantly with postnatal age. We conclude that in the
rat: (1) CYP2B and NADPH reductase distribution and CYP2B activity
are age-dependent; (2) the increase in Clara cell SER precedes the
expression of CYP2B protein; (3) cellular appearance of CYP2B protein
precedes CYP activity; and (4) SER appearance and P450 protein
expression do not occur uniformly in differentiating Clara cells,
even within the same bronchiole.
Received 9 February 1995; accepted in final form 5 May 1995.
APS Manuscript Number L48-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.