Aminoglutethimide-induced lysosomal changes in adrenal gland in mice

Q2 Medicine Experimental and Toxicologic Pathology Pub Date : 2017-09-05 DOI:10.1016/j.etp.2017.04.004

Mayu Mutsuga, Yoshiji Asaoka, Naoko Imura, Tomoya Miyoshi, Yuko Togashi

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引用次数: 3

Abstract

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.

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氨基乙硫胺诱导小鼠肾上腺溶酶体改变

氨基乙硫胺是一种甾体生成抑制剂，抑制胆固醇侧链切割酶(CYP11A1)，该酶在线粒体中将胆固醇转化为孕烯醇酮。我们观察了AG给药5 d后小鼠的组织病理学变化。ag处理小鼠的束带细胞出现大小不等的细胞质空泡和单细胞坏死。免疫组化染色部分液泡亲脂蛋白阳性，部分液泡溶酶体相关膜蛋白-2阳性，分别为增大的脂滴和溶酶体。电镜观察发现束状带细胞内溶酶体增大，含有受损的线粒体和板层体，认为这反映了细胞内蛋白质降解过程、线粒体自噬和脂肪吞噬。从这些结果中，我们发现AG诱导束状带细胞过度的脂质积累和线粒体损伤，从而导致小鼠溶酶体降解加速。

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来源期刊

Experimental and Toxicologic Pathology 医学-病理学

CiteScore

2.08

自引率

0.00%

发文量

审稿时长

5.3 weeks

期刊介绍： Cessation. The international multidisciplinary journal is devoted to the publication of studies covering the whole range of experimental research on disease processes and toxicology including cell biological investigations. Its aim is to support progress in the interdisciplinary cooperation of researchers working in pathobiology, toxicology, and cell biology independent of the methods applied. During the past decades increasing attention has been paid to the importance of toxic influence in the pathogenesis of human and animal diseases. This is why Experimental and Toxicologic Pathology meets the urgent need for an interdisciplinary journal felt by a wide variety of experts in medicine and biology, including pathologists, toxicologists, biologists, physicians, veterinary surgeons, pharmacists, and pharmacologists working in academic, industrial or clinical institutions.