Aminoglutethimide-induced lysosomal changes in adrenal gland in mice
Aminoglutethimide is a steroidogenesis inhibitor and inhibits a cholesterol side-chain cleavage enzyme (CYP11A1) that converts cholesterol to pregnenolone in mitochondria. We investigated histopathological changes induced by 5-day administration of AG in mice. Cytoplasmic vacuoles of various sizes a...
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Veröffentlicht in: | Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2017-09, Vol.69 (7), p.424-429 |
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container_title | Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie |
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creator | Mutsuga, Mayu Asaoka, Yoshiji Imura, Naoko Miyoshi, Tomoya Togashi, Yuko |
description | Aminoglutethimide is a steroidogenesis inhibitor and inhibits a cholesterol side-chain cleavage enzyme (CYP11A1) that converts cholesterol to pregnenolone in mitochondria. We investigated histopathological changes induced by 5-day administration of AG in mice. Cytoplasmic vacuoles of various sizes and single cell necrosis were found in zona fasciculata cells in AG-treated mice. Some vacuoles were positive for adipophilin, whereas others were positive for lysosome-associated membrane protein-2 on immunohistochemical staining, indicating they were enlarged lipid droplets and lysosomes, respectively. Electron microscopy revealed enlarged lysosomes containing damaged mitochondria and lamellar bodies in zona fasciculata cells, and they were considered to reflect the intracellular protein degradation processes, mitophagy and lipophagy. From these results, we showed that AG induces excessive lipid accumulation and mitochondrial damage in zona fasciculata cells, which leads to an accelerated lysosomal degradation in mice. |
doi_str_mv | 10.1016/j.etp.2017.04.004 |
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We investigated histopathological changes induced by 5-day administration of AG in mice. Cytoplasmic vacuoles of various sizes and single cell necrosis were found in zona fasciculata cells in AG-treated mice. Some vacuoles were positive for adipophilin, whereas others were positive for lysosome-associated membrane protein-2 on immunohistochemical staining, indicating they were enlarged lipid droplets and lysosomes, respectively. Electron microscopy revealed enlarged lysosomes containing damaged mitochondria and lamellar bodies in zona fasciculata cells, and they were considered to reflect the intracellular protein degradation processes, mitophagy and lipophagy. From these results, we showed that AG induces excessive lipid accumulation and mitochondrial damage in zona fasciculata cells, which leads to an accelerated lysosomal degradation in mice.</description><identifier>ISSN: 0940-2993</identifier><identifier>EISSN: 1618-1433</identifier><identifier>DOI: 10.1016/j.etp.2017.04.004</identifier><identifier>PMID: 28410883</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Adrenal Glands - drug effects ; Adrenal Glands - pathology ; Adrenal toxicity ; Aminoglutethimide ; Aminoglutethimide - toxicity ; Animals ; Aromatase Inhibitors - toxicity ; Autophagy ; Lysosomes - drug effects ; Lysosomes - pathology ; Male ; Mice ; Mouse</subject><ispartof>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, 2017-09, Vol.69 (7), p.424-429</ispartof><rights>2017 Elsevier GmbH</rights><rights>Copyright © 2017 Elsevier GmbH. 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subjects | Adrenal Glands - drug effects Adrenal Glands - pathology Adrenal toxicity Aminoglutethimide Aminoglutethimide - toxicity Animals Aromatase Inhibitors - toxicity Autophagy Lysosomes - drug effects Lysosomes - pathology Male Mice Mouse |
title | Aminoglutethimide-induced lysosomal changes in adrenal gland in mice |
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