Next Article in Journal
Genome-Wide Identification of Polyamine Oxidase (PAO) Family Genes: Roles of CaPAO2 and CaPAO4 in the Cold Tolerance of Pepper (Capsicum annuum L.)
Next Article in Special Issue
Glycogen—Endoplasmic Reticulum Connection in the Liver
Previous Article in Journal
Dynamic and Static Switching in ITO/SnOx/ITO and Its Synaptic Application
Previous Article in Special Issue
A Mouse Model of Glycogen Storage Disease Type IX-Beta: A Role for Phkb in Glycogenolysis
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 23
Issue 17
10.3390/ijms23179996
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation

by
Francesco Callea
1,*,
Paola Francalanci
2,
Chiara Grimaldi
3,
Francesca Diomedi Camassei
2,
Rita Devito
2,
Fabio Facchetti
4,
Rita Alaggio
2 and
Emanuele Bellacchio
5
1
Department of Pathology, Catholic University Bugando Medical Centre, Mwanza P.O. Box 1464, Tanzania
2
Pathology Unit, Department of Laboratories, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
3
Department of Surgery, Children Hospital Meyer, 50139 Florence, Italy
4
Department of Pathology University of Brescia Spedali Civili, 25121 Brescia, Italy
5
Area di Ricerca Genetica e Malattie Rare, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(17), 9996; https://doi.org/10.3390/ijms23179996
Submission received: 1 July 2022 / Revised: 27 July 2022 / Accepted: 3 August 2022 / Published: 2 September 2022
(This article belongs to the Special Issue Glycogen and Liver)
Browse Figures
Review Reports Versions Notes

Abstract

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.
Keywords: glycogen-ground glass; polyglucosan bodies; hepatocytes; drugs glycogen-ground glass; polyglucosan bodies; hepatocytes; drugs

Share and Cite

MDPI and ACS Style

Callea, F.; Francalanci, P.; Grimaldi, C.; Camassei, F.D.; Devito, R.; Facchetti, F.; Alaggio, R.; Bellacchio, E. Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation. Int. J. Mol. Sci. 2022, 23, 9996. https://doi.org/10.3390/ijms23179996

AMA Style

Callea F, Francalanci P, Grimaldi C, Camassei FD, Devito R, Facchetti F, Alaggio R, Bellacchio E. Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation. International Journal of Molecular Sciences. 2022; 23(17):9996. https://doi.org/10.3390/ijms23179996

Chicago/Turabian Style

Callea, Francesco, Paola Francalanci, Chiara Grimaldi, Francesca Diomedi Camassei, Rita Devito, Fabio Facchetti, Rita Alaggio, and Emanuele Bellacchio. 2022. "Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation" International Journal of Molecular Sciences 23, no. 17: 9996. https://doi.org/10.3390/ijms23179996

APA Style

Callea, F., Francalanci, P., Grimaldi, C., Camassei, F. D., Devito, R., Facchetti, F., Alaggio, R., & Bellacchio, E. (2022). Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation. International Journal of Molecular Sciences, 23(17), 9996. https://doi.org/10.3390/ijms23179996

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop