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Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation
Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor’s liver. Under the electron microscope (EM), the stored material within the cytosol appeared...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456521/ https://www.ncbi.nlm.nih.gov/pubmed/36077394 http://dx.doi.org/10.3390/ijms23179996 |
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author | Callea, Francesco Francalanci, Paola Grimaldi, Chiara Camassei, Francesca Diomedi Devito, Rita Facchetti, Fabio Alaggio, Rita Bellacchio, Emanuele |
author_facet | Callea, Francesco Francalanci, Paola Grimaldi, Chiara Camassei, Francesca Diomedi Devito, Rita Facchetti, Fabio Alaggio, Rita Bellacchio, Emanuele |
author_sort | Callea, Francesco |
collection | PubMed |
description | Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor’s liver. Under the electron microscope (EM), the stored material within the cytosol appeared as non-membrane-bound aggregates of electron-lucent globoid or fibrillar granules, previously described as abnormally structured glycogen and identified as Polyglucosan bodies (PB). The appearance of GGG in our children was analogous to that of PB-GGG occurring in a number of congenital diseases due to gene mutations such as Lafora’s d., Andersen’s d., Adult Polyglucosan Body Disease and glycogenin deficiency. The same type of GGG was previously reported in the liver of patients undergoing transplants, immunosuppressive or antiblastic treatment. To explore the potential mechanism of GGG formation, we examined whether the drugs after whose treatment this phenomenon was observed could have a role. By carrying out molecular docking, we found that such drugs somehow present a high binding affinity for the active region of glycogenin, implicating that they can inactivate the protein, thus preventing its interaction with glycogen synthase (GS), as well as the maturation of the nascent glycogen towards gamma, beta or alfa glycogen granules. We could also demonstrate that PG inclusions consist of a complex of PAS positive material (glycogen) and glycogen-associated proteins, i.e., glicogenin-1 and -2 and ubiquitin. These features appear to be analogous to congenital GGG, suggesting that, in both cases, they result from the simultaneous dysregulation of glycogen synthesis and degradation. Drug-induced GGG appear to be toxic to the cell, despite their reversibility. |
format | Online Article Text |
id | pubmed-9456521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94565212022-09-09 Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation Callea, Francesco Francalanci, Paola Grimaldi, Chiara Camassei, Francesca Diomedi Devito, Rita Facchetti, Fabio Alaggio, Rita Bellacchio, Emanuele Int J Mol Sci Article Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor’s liver. Under the electron microscope (EM), the stored material within the cytosol appeared as non-membrane-bound aggregates of electron-lucent globoid or fibrillar granules, previously described as abnormally structured glycogen and identified as Polyglucosan bodies (PB). The appearance of GGG in our children was analogous to that of PB-GGG occurring in a number of congenital diseases due to gene mutations such as Lafora’s d., Andersen’s d., Adult Polyglucosan Body Disease and glycogenin deficiency. The same type of GGG was previously reported in the liver of patients undergoing transplants, immunosuppressive or antiblastic treatment. To explore the potential mechanism of GGG formation, we examined whether the drugs after whose treatment this phenomenon was observed could have a role. By carrying out molecular docking, we found that such drugs somehow present a high binding affinity for the active region of glycogenin, implicating that they can inactivate the protein, thus preventing its interaction with glycogen synthase (GS), as well as the maturation of the nascent glycogen towards gamma, beta or alfa glycogen granules. We could also demonstrate that PG inclusions consist of a complex of PAS positive material (glycogen) and glycogen-associated proteins, i.e., glicogenin-1 and -2 and ubiquitin. These features appear to be analogous to congenital GGG, suggesting that, in both cases, they result from the simultaneous dysregulation of glycogen synthesis and degradation. Drug-induced GGG appear to be toxic to the cell, despite their reversibility. MDPI 2022-09-02 /pmc/articles/PMC9456521/ /pubmed/36077394 http://dx.doi.org/10.3390/ijms23179996 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Callea, Francesco Francalanci, Paola Grimaldi, Chiara Camassei, Francesca Diomedi Devito, Rita Facchetti, Fabio Alaggio, Rita Bellacchio, Emanuele Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation |
title | Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation |
title_full | Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation |
title_fullStr | Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation |
title_full_unstemmed | Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation |
title_short | Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation |
title_sort | pathomorphogenesis of glycogen-ground glass hepatocytic inclusions (polyglucosan bodies) in children after liver transplantation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456521/ https://www.ncbi.nlm.nih.gov/pubmed/36077394 http://dx.doi.org/10.3390/ijms23179996 |
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