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Journal of Lipid Research, Vol 30, 1859-1875, Copyright © 1989 by Lipid Research, Inc.
Zonal heterogeneity of peroxisome proliferation and morphology in rat liver after gemfibrozil treatment
K Gorgas and SK Krisans
Department of Anatomy and Cell Biology, University of Heidelberg, FRG.
The effect of gemfibrozil on the fine structure of peroxisomes across the
rat liver lobule was investigated by light and electron microscopy using
the alkaline diaminobenzidine (DAB) medium for the visualization of
catalase peroxidatic activity. The oral administration of gemfibrozil for 2
weeks induces a striking heterogeneity in the lobular distribution of
peroxisomes. The size and shape of peroxisomes, variety of matrix
modifications, catalase content, and position within the cell, are
functions of the zonal localization of the hepatocytes. The largest and
most numerous peroxisomes were found in the centrilobular region indicating
that these cells are most sensitive to peroxisome proliferation. On the
other hand, the greatest variety of peroxisome shapes and matrix
alterations (tubules and plates) was seen more peripherally in the
mid-zonal and periportal regions. The larger, round centrilobular
peroxisomes stained less intensely than the elongated peroxisomes found
more peripherally, indicating a discrepancy between peroxisome size and
catalase content. A distinct population of small irregularly shaped
peroxisomes, lacking matrix specializations and containing variable
catalase content, was found in the mid-zonal region. Peroxisomes in the
centrilobular region were located within areas of the cell containing SER
and glycogen while those in the more peripheral region were relegated to
areas of the cytoplasm separate from RER and SER. In addition to
modifications of peroxisomes, gemfibrozil treatment resulted in a
proliferation and formation of whorled configurations of SER. This was
particularly evident in the mid- zonal region, where single peroxisomal
profiles could be seen surrounded by whorls of SER membranes. The results
suggest that rat liver hepatocytes of the centrilobular region are the most
sensitive to peroxisome proliferation and those of the periportal area are
most susceptible to peroxisome matrix alterations after gemfibrozil
treatment.

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Copyright © 1989 by the American Society for Biochemistry and Molecular Biology.
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