Proliferation of myocardial peroxisomes caused by several agents and conditions.
In view of considerable gaps in our knowledge of myocardial peroxisomes. the aim of the present study is, on the basis of extensive electron-microscopic investigations, to provide reliable results on the inducibility of a proliferation (increase in the number) of these organelles in rodents' heart by several agents and conditions. As far as possible, we compared the response of heart and liver peroxisomes. Morphometric investigations were performed to assess the effectiveness of the hypolipidemic agent HL 41, erucic acid, ethanol, nifedipine, chlorpromazine, two cardiotonic drugs, isoprenaline, adriamycin, and physical exercise. The study also included spontaneously hypertensive rats (SHR). A further objective was to determine synergistic or additive effects that might occur when two or three peroxisome-proliferating stimuli act simultaneously. In every case we observed a clear peroxisome proliferation, which was found to increase by between 10 and 97% under the influence of an additional inducer. The observed increase in peroxisome number ranged from almost 200% to nearly 400%. Our results suggest that very different agents and conditions can induce myocardial peroxisome proliferation when they lead to metabolic alterations associated with an increased need for a peroxisomal beta-oxidation of fatty acids as an energy source and/or for preventing toxic effects. Regulatory mechanisms of these adaptive processes are apparently also present in the heart via peroxisome proliferator-activated receptors (PPARs) and their activation by fatty acids, which can also stimulate the PPARs gene expression. The assumption that stimulated catalase gene expression might be responsible for the induction of peroxisome proliferation as a cellular response to an extraperoxisomal oxidative stress situation (isoprenaline, adriamycin, or physical exercise) poses some critical questions. These questions pertain especially to: (a) quantitative aspects with regard to the possible effectiveness of an increase in catalase activity by two-, three-, or four-fold enhanced peroxisome numbers; (b) the role of cytoplasmic catalase; (c) the existence and importance of a myocardial mitochondrial catalase; and (d) the co-operation between the two H2O2-destroying enzymes catalase and glutathione peroxidase.
Zipper
J
J
Institute for Molecular Pharmacology, Berlin, Germany.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004883:Erucic Acids / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006973:Hypertension / Q000473:pathology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008830:Microbodies / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure; D005082:Physical Exertion / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D015203:Reproducibility of Results
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D004883:Erucic Acids; D000960:Hypolipidemic Agents; C049811:erucic acid