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毒性损伤后肝细胞细胞骨架的重排:停药后马洛里小体物质的退化、分散和外周聚集。

Rearrangement of the hepatocyte cytoskeleton after toxic damage: involution, dispersal and peripheral accumulation of Mallory body material after drug withdrawal.

作者信息

Denk H, Franke W W

出版信息

Eur J Cell Biol. 1981 Feb;23(2):241-9.

PMID:7193580
Abstract

Large cytoplasmic aggregates (Mallory bodies) containing randomly arranged 10 to 20 nm thick filaments are characteristic structures of hepatocytes in certain liver diseases, especially alcoholic hepatitis of man and griseofulvin intoxication of mouse. Biochemical and immunological studies have shown that such Mallory bodies contain structural proteins related to the cytokeratins present in epithelial cells of various kinds, normal hepatocytes included. We have studied the mode of reorganization of the hepatocyte cytoskeleton during involution of Mallory bodies experimentally induced in mice by prolonged griseofulvin feeding after withdrawal of the drug, using immunofluorescence microscopy and electron microscopy. Dispersal of Mallory bodies into small granules accumulating in the hepatocyte periphery is a characteristic feature of Mallory body involution. Dispersed heaps of Mallory body material are seen in hepatocyte cortices at lateral (hepatocyte-to-hepatocyte) as well as at sinusoidal cell surfaces. Mallory body material dispersed to the cell periphery exhibits a filamentous ultrastructure an often shows conspicuous associations with desmosomes. Three different types of desmosome complexes can be discriminated in livers of mice allowed to recover from the intoxication: (i) desmosomes with normally looking bundles of tonofilaments; (ii) desmosomes associated with Mallory body filaments but few, if any, tono-filaments; and (iii) desmosomes lacking tonofilaments as well as Mallory body filaments. The associations between Mallory body filaments and desmosomes during Mallory body involution further strengthen the relationship between Mallory body filaments and tonofilaments. The observations suggest that Mallory body material, at least in part, may be utilized for rearrangement of the hepatocyte cytoskeleton, especially tonofilament-desmosome complexes.

摘要

大型细胞质聚集体(马洛里小体)含有随机排列的10至20纳米厚的细丝,是某些肝脏疾病中肝细胞的特征性结构,尤其是人类酒精性肝炎和小鼠灰黄霉素中毒。生化和免疫学研究表明,这种马洛里小体含有与各种上皮细胞(包括正常肝细胞)中存在的细胞角蛋白相关的结构蛋白。我们使用免疫荧光显微镜和电子显微镜,研究了在给小鼠长期喂食灰黄霉素后停药,实验诱导产生的马洛里小体退化过程中肝细胞细胞骨架的重组模式。马洛里小体分散成积聚在肝细胞周边的小颗粒是马洛里小体退化的一个特征。在肝细胞侧面(肝细胞与肝细胞之间)以及窦状细胞表面的肝细胞皮质中可见分散的马洛里小体物质堆。分散到细胞周边的马洛里小体物质呈现丝状超微结构,并且常常与桥粒有明显的联系。在从中毒中恢复的小鼠肝脏中可以区分出三种不同类型的桥粒复合体:(i)具有外观正常的张力丝束的桥粒;(ii)与马洛里小体细丝相关但几乎没有张力丝的桥粒;(iii)既没有张力丝也没有马洛里小体细丝的桥粒。在马洛里小体退化过程中,马洛里小体细丝与桥粒之间的联系进一步加强了马洛里小体细丝与张力丝之间的关系。这些观察结果表明,马洛里小体物质至少部分可用于肝细胞细胞骨架的重排,尤其是张力丝 - 桥粒复合体。

相似文献

1
Rearrangement of the hepatocyte cytoskeleton after toxic damage: involution, dispersal and peripheral accumulation of Mallory body material after drug withdrawal.毒性损伤后肝细胞细胞骨架的重排:停药后马洛里小体物质的退化、分散和外周聚集。
Eur J Cell Biol. 1981 Feb;23(2):241-9.
2
Relationship of Mallory bodies to the cytoskeleton of hepatocytes in griseofulvin-treated mice.灰黄霉素处理小鼠中马洛里小体与肝细胞细胞骨架的关系。
Lab Invest. 1982 Oct;47(4):336-45.
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Maintenance of desmosomes in mouse hepatocytes after drug-induced rearrangement of cytokeratin filament material. Demonstration of independence of desmosomes and intermediate-sized filaments.药物诱导细胞角蛋白丝物质重排后小鼠肝细胞中桥粒的维持。桥粒与中间丝独立性的证明。
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Ultrastructural, biochemical, and immunologic characterization of Mallory bodies in livers of griseofulvin-treated mice. Fimbriated rods of filaments containing prekeratin-like polypeptides.灰黄霉素处理小鼠肝脏中马洛里小体的超微结构、生化及免疫学特征。含前角蛋白样多肽的丝状菌毛棒。
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Electron microscopic study of the in vitro calcium-dependent degradation of Mallory bodies and intermediate filaments in hepatocytes.肝细胞中马洛里小体和中间丝体外钙依赖性降解的电子显微镜研究
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Disturbance of keratin homeostasis in griseofulvin-intoxicated mouse liver.灰黄霉素中毒小鼠肝脏中角蛋白稳态的紊乱
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Formation and involution of Mallory bodies ("alcoholic hyalin") in murine and human liver revealed by immunofluorescence microscopy with antibodies to prekeratin.用抗前角蛋白抗体通过免疫荧光显微镜观察小鼠和人肝脏中马洛里小体(“酒精性透明小体”)的形成与消退。
Proc Natl Acad Sci U S A. 1979 Aug;76(8):4112-6. doi: 10.1073/pnas.76.8.4112.
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Relationship of Mallory bodies to intermediate filaments in hepatocytes. A scanning electron microscopy study.马洛里小体与肝细胞中间丝的关系。扫描电子显微镜研究。
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Fate of Mallory body-containing hepatocytes: disappearance of Mallory bodies and restoration of the hepatocytic intermediate filament cytoskeleton after drug withdrawal in the griseofulvin-treated mouse.
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Ubiquitin is present on the cytokeratin intermediate filaments and Mallory bodies of hepatocytes.泛素存在于细胞角蛋白中间丝和肝细胞的马洛里小体上。
Lab Invest. 1988 Dec;59(6):848-56.

引用本文的文献

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p62/Sequestosome-1 Is Indispensable for Maturation and Stabilization of Mallory-Denk Bodies.p62/聚集体蛋白-1对马洛里-丹科小体的成熟和稳定至关重要。
PLoS One. 2016 Aug 15;11(8):e0161083. doi: 10.1371/journal.pone.0161083. eCollection 2016.
2
The role of the ubiquitin proteasome pathway in keratin intermediate filament protein degradation.泛素蛋白酶体途径在角蛋白中间丝蛋白降解中的作用。
Proc Am Thorac Soc. 2010 Feb;7(1):71-6. doi: 10.1513/pats.200908-089JS.
3
A cell culture system for the induction of Mallory bodies: Mallory bodies and aggresomes represent different types of inclusion bodies.
一种用于诱导马洛里小体的细胞培养系统:马洛里小体和聚集体代表不同类型的包涵体。
Histochem Cell Biol. 2009 Sep;132(3):293-304. doi: 10.1007/s00418-009-0598-9. Epub 2009 Apr 18.
4
S-adenosylmethionine prevents Mallory Denk body formation in drug-primed mice by inhibiting the epigenetic memory.S-腺苷甲硫氨酸通过抑制表观遗传记忆来预防药物引发的小鼠中马洛里小体的形成。
Hepatology. 2008 Feb;47(2):613-24. doi: 10.1002/hep.22029.
5
Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies.细胞角蛋白8可保护细胞免受肝毒性影响,其与细胞角蛋白18的比例决定了肝细胞形成马洛里小体的能力。
Am J Pathol. 2000 Apr;156(4):1263-74. doi: 10.1016/S0002-9440(10)64997-8.
6
Intermediate filaments as dynamic structures.作为动态结构的中间丝
Cancer Metastasis Rev. 1996 Dec;15(4):417-28. doi: 10.1007/BF00054010.
7
Alterations in the organisation of cytokeratin filaments in normal and malignant human colonic epithelial cells during mitosis.
Cell Tissue Res. 1983;233(3):619-28. doi: 10.1007/BF00212229.
8
Cytoarchitectural analysis of epithelial sheets formed in vitro by hepatic tumor cells possessing defined intermediate-sized filament cytoskeletal abnormalities.对具有特定中间丝细胞骨架异常的肝癌细胞在体外形成的上皮细胞片进行细胞结构分析。
Am J Pathol. 1989 Feb;134(2):447-56.
9
Altered cytokeratin expression and differentiation induction during neoplastic transformation of cultured rat liver cells by nickel subsulfide.硫化镍诱导培养大鼠肝细胞肿瘤转化过程中细胞角蛋白表达的改变及分化诱导
Cell Biol Toxicol. 1989 Nov;5(3):271-86. doi: 10.1007/BF01795356.