Hallmarks of oxidative stress in the livers of aged mice with mild glycogen branching enzyme deficiency
Copyright © 2020 Elsevier Inc. All rights reserved..
Glycogen branching enzyme (GBE1) introduces branching points in the glycogen molecule during its synthesis. Pathogenic GBE1 gene mutations lead to glycogen storage disease type IV (GSD IV), which is characterized by excessive intracellular accumulation of abnormal, poorly branched glycogen in affected tissues and organs, mostly in the liver. Using heterozygous Gbe1 knock-out mice (Gbe1+/-), we analyzed the effects of moderate GBE1 deficiency on oxidative stress in the liver. The livers of aged Gbe1+/- mice (22 months old) had decreased GBE1 protein levels, which caused a mild decrease in the degree of glycogen branching, but did not affect the tissue glycogen content. GBE1 deficiency was accompanied by increased protein carbonylation and elevated oxidation of the glutathione pool, indicating the existence of oxidative stress. Furthermore, we have observed increased levels of glutathione peroxidase and decreased activity of respiratory complex I in Gbe1+/- livers. Our data indicate that even mild changes in the degree of glycogen branching, which did not lead to excessive glycogen accumulation, may have broader effects on cellular bioenergetics and redox homeostasis. In young animals cellular homeostatic mechanisms are able to counteract those changes, while in aged tissues the changes may lead to increased oxidative stress.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:695 |
|---|---|
| Enthalten in: |
Archives of biochemistry and biophysics - 695(2020) vom: 30. Nov., Seite 108626 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Malinska, Dominika [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.12.2020 Date Revised 14.12.2020 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.abb.2020.108626 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM316189510 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM316189510 | ||
| 003 | DE-627 | ||
| 005 | 20231225160538.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.abb.2020.108626 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1053.xml |
| 035 | |a (DE-627)NLM316189510 | ||
| 035 | |a (NLM)33049291 | ||
| 035 | |a (PII)S0003-9861(20)30635-4 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Malinska, Dominika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hallmarks of oxidative stress in the livers of aged mice with mild glycogen branching enzyme deficiency |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.12.2020 | ||
| 500 | |a Date Revised 14.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a Glycogen branching enzyme (GBE1) introduces branching points in the glycogen molecule during its synthesis. Pathogenic GBE1 gene mutations lead to glycogen storage disease type IV (GSD IV), which is characterized by excessive intracellular accumulation of abnormal, poorly branched glycogen in affected tissues and organs, mostly in the liver. Using heterozygous Gbe1 knock-out mice (Gbe1+/-), we analyzed the effects of moderate GBE1 deficiency on oxidative stress in the liver. The livers of aged Gbe1+/- mice (22 months old) had decreased GBE1 protein levels, which caused a mild decrease in the degree of glycogen branching, but did not affect the tissue glycogen content. GBE1 deficiency was accompanied by increased protein carbonylation and elevated oxidation of the glutathione pool, indicating the existence of oxidative stress. Furthermore, we have observed increased levels of glutathione peroxidase and decreased activity of respiratory complex I in Gbe1+/- livers. Our data indicate that even mild changes in the degree of glycogen branching, which did not lead to excessive glycogen accumulation, may have broader effects on cellular bioenergetics and redox homeostasis. In young animals cellular homeostatic mechanisms are able to counteract those changes, while in aged tissues the changes may lead to increased oxidative stress | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Glycogen | |
| 650 | 4 | |a Glycogen branching enzyme | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 7 | |a Glycogen Debranching Enzyme System |2 NLM | |
| 650 | 7 | |a Glycogen |2 NLM | |
| 650 | 7 | |a 9005-79-2 |2 NLM | |
| 650 | 7 | |a Glutathione Peroxidase |2 NLM | |
| 650 | 7 | |a EC 1.11.1.9 |2 NLM | |
| 650 | 7 | |a Electron Transport Complex I |2 NLM | |
| 650 | 7 | |a EC 7.1.1.2 |2 NLM | |
| 700 | 1 | |a Testoni, Giorgia |e verfasserin |4 aut | |
| 700 | 1 | |a Duran, Jordi |e verfasserin |4 aut | |
| 700 | 1 | |a Brudnicka, Alicja |e verfasserin |4 aut | |
| 700 | 1 | |a Guinovart, Joan J |e verfasserin |4 aut | |
| 700 | 1 | |a Duszynski, Jerzy |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Archives of biochemistry and biophysics |d 1951 |g 695(2020) vom: 30. Nov., Seite 108626 |w (DE-627)NLM000012998 |x 1096-0384 |7 nnns |
| 773 | 1 | 8 | |g volume:695 |g year:2020 |g day:30 |g month:11 |g pages:108626 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.abb.2020.108626 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 695 |j 2020 |b 30 |c 11 |h 108626 | ||