title: The role of 15-lipoxygenase in disruption of the peroxisomal membrane and in programmed degradation of peroxisomes in normal rat liver.
abstract: Our earlier electron microscopic observations revealed that prolonged exposure of glutaraldehyde-fixed rat liver sections to buffer solutions induced focal membrane disruptions of peroxisomes with catalase diffusion as shown cytochemically. Recently, it was suggested that 15-lipoxygenase (15-LOX) might be involved in natural degradation of membrane-bound organelles in reticulocytes by integrating into and permeabilizing the organelle membranes, leading to the release of matrix proteins. We have now investigated the localization of 15-LOX and its role in degradation of peroxisomal membranes in rat liver. Aldehyde-fixed liver slices were incubated in a medium that conserved the 15-LOX activity, consisting of 50 mM HEPES-KOH buffer (pH 7.4), 5 mM mercaptoethanol, 1 mM MgCl(2), 15 mM NaN(3), and 0.2 M sucrose, in presence or absence of 0.5-0.05 mM propyl gallate or esculetin, two inhibitors of 15-LOX. The exposure of aldehyde-fixed liver sections to this medium induced focal disruptions of peroxisome membranes and catalase diffusion around some but not all peroxisomes. This was significantly reduced by both 15-LOX inhibitors, propyl gallate and esculetin, with the latter being more effective. Double immunofluorescent staining for 15-LOX and catalase revealed that 15-LOX was co-localized with catalase in some but not all peroxisomes in rat hepatocytes. By postembedding immunoelectron microscopy, gold labeling was localized on membranes of some peroxisomes. These observations suggest that 15-LOX is involved in degradation of peroxisomal membranes and might have a physiological role in programmed degradation and turnover of peroxisomes in hepatocytes. (J Histochem Cytochem 49:613-621, 2001)
authors: Biology Laboratory, Yamanashi Medical University, Yamanashi 409-3898, Japan. syokota@res.yamanashi-med.ac.jp
authors: S
authors: S
authors: Yokota
authors: T
authors: T
authors: Oda
authors: H D
authors: HD
authors: Fahimi
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D002451:Cell Compartmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000201:enzymology / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008099:Liver / Q000648:ultrastructure*; D016253:Microscopy, Immunoelectron; D008930:Mitochondria, Liver / Q000201:enzymology; D020675:Peroxisomes / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D002374:Catalase; D001093:Arachidonate 15-Lipoxygenase