Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition
Heme oxygenase 1 (Hmox1), a ubiquitous enzyme degrading heme to carbon monoxide, iron, and biliverdin, is one of the cytoprotective enzymes induced in response to a variety of stimuli, including cellular oxidative stress. Gangliosides, sialic acid-containing glycosphingolipids expressed in all cells...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2018-01-01
|
Series: | Oxidative Medicine and Cellular Longevity |
Online Access: | http://dx.doi.org/10.1155/2018/3845027 |
id |
doaj-bb3ad692a0514cbe8de3902b10c3cb15 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Václav Šmíd Jakub Šuk Neli Kachamakova-Trojanowska Jana Jašprová Petra Valášková Alicja Józkowicz Józef Dulak František Šmíd Libor Vítek Lucie Muchová |
spellingShingle |
Václav Šmíd Jakub Šuk Neli Kachamakova-Trojanowska Jana Jašprová Petra Valášková Alicja Józkowicz Józef Dulak František Šmíd Libor Vítek Lucie Muchová Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition Oxidative Medicine and Cellular Longevity |
author_facet |
Václav Šmíd Jakub Šuk Neli Kachamakova-Trojanowska Jana Jašprová Petra Valášková Alicja Józkowicz Józef Dulak František Šmíd Libor Vítek Lucie Muchová |
author_sort |
Václav Šmíd |
title |
Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition |
title_short |
Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition |
title_full |
Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition |
title_fullStr |
Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition |
title_full_unstemmed |
Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition |
title_sort |
heme oxygenase-1 may affect cell signalling via modulation of ganglioside composition |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2018-01-01 |
description |
Heme oxygenase 1 (Hmox1), a ubiquitous enzyme degrading heme to carbon monoxide, iron, and biliverdin, is one of the cytoprotective enzymes induced in response to a variety of stimuli, including cellular oxidative stress. Gangliosides, sialic acid-containing glycosphingolipids expressed in all cells, are involved in cell recognition, signalling, and membrane stabilization. Their expression is often altered under many pathological and physiological conditions including cell death, proliferation, and differentiation. The aim of this study was to assess the possible role of Hmox1 in ganglioside metabolism in relation to oxidative stress. The content of liver and brain gangliosides, their cellular distribution, and mRNA as well as protein expression of key glycosyltransferases were determined in Hmox1 knockout mice as well as their wild-type littermates. To elucidate the possible underlying mechanisms between Hmox1 and ganglioside metabolism, hepatoblastoma HepG2 and neuroblastoma SH-SY5Y cell lines were used for in vitro experiments. Mice lacking Hmox1 exhibited a significant increase in concentrations of liver and brain gangliosides and in mRNA expression of the key enzymes of ganglioside metabolism. A marked shift of GM1 ganglioside from the subsinusoidal part of the intracellular compartment into sinusoidal membranes of hepatocytes was shown in Hmox1 knockout mice. Induction of oxidative stress by chenodeoxycholic acid in vitro resulted in a significant increase in GM3, GM2, and GD1a gangliosides in SH-SY5Y cells and GM3 and GM2 in the HepG2 cell line. These changes were abolished with administration of bilirubin, a potent antioxidant agent. These observations were closely related to oxidative stress-mediated changes in sialyltransferase expression regulated at least partially through the protein kinase C pathway. We conclude that oxidative stress is an important factor modulating synthesis and distribution of gangliosides in vivo and in vitro which might affect ganglioside signalling in higher organisms. |
url |
http://dx.doi.org/10.1155/2018/3845027 |
work_keys_str_mv |
AT vaclavsmid hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT jakubsuk hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT nelikachamakovatrojanowska hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT janajasprova hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT petravalaskova hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT alicjajozkowicz hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT jozefdulak hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT frantiseksmid hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT liborvitek hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition AT luciemuchova hemeoxygenase1mayaffectcellsignallingviamodulationofgangliosidecomposition |
_version_ |
1725092236129992704 |
spelling |
doaj-bb3ad692a0514cbe8de3902b10c3cb152020-11-25T01:30:18ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942018-01-01201810.1155/2018/38450273845027Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside CompositionVáclav Šmíd0Jakub Šuk1Neli Kachamakova-Trojanowska2Jana Jašprová3Petra Valášková4Alicja Józkowicz5Józef Dulak6František Šmíd7Libor Vítek8Lucie Muchová9Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 32, 12108 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 32, 12108 Prague, Czech RepublicDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 7 Gronostajowa St., 30-387 Krakow, PolandInstitute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 32, 12108 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 32, 12108 Prague, Czech RepublicDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 7 Gronostajowa St., 30-387 Krakow, PolandDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 7 Gronostajowa St., 30-387 Krakow, PolandInstitute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 32, 12108 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 32, 12108 Prague, Czech RepublicInstitute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 32, 12108 Prague, Czech RepublicHeme oxygenase 1 (Hmox1), a ubiquitous enzyme degrading heme to carbon monoxide, iron, and biliverdin, is one of the cytoprotective enzymes induced in response to a variety of stimuli, including cellular oxidative stress. Gangliosides, sialic acid-containing glycosphingolipids expressed in all cells, are involved in cell recognition, signalling, and membrane stabilization. Their expression is often altered under many pathological and physiological conditions including cell death, proliferation, and differentiation. The aim of this study was to assess the possible role of Hmox1 in ganglioside metabolism in relation to oxidative stress. The content of liver and brain gangliosides, their cellular distribution, and mRNA as well as protein expression of key glycosyltransferases were determined in Hmox1 knockout mice as well as their wild-type littermates. To elucidate the possible underlying mechanisms between Hmox1 and ganglioside metabolism, hepatoblastoma HepG2 and neuroblastoma SH-SY5Y cell lines were used for in vitro experiments. Mice lacking Hmox1 exhibited a significant increase in concentrations of liver and brain gangliosides and in mRNA expression of the key enzymes of ganglioside metabolism. A marked shift of GM1 ganglioside from the subsinusoidal part of the intracellular compartment into sinusoidal membranes of hepatocytes was shown in Hmox1 knockout mice. Induction of oxidative stress by chenodeoxycholic acid in vitro resulted in a significant increase in GM3, GM2, and GD1a gangliosides in SH-SY5Y cells and GM3 and GM2 in the HepG2 cell line. These changes were abolished with administration of bilirubin, a potent antioxidant agent. These observations were closely related to oxidative stress-mediated changes in sialyltransferase expression regulated at least partially through the protein kinase C pathway. We conclude that oxidative stress is an important factor modulating synthesis and distribution of gangliosides in vivo and in vitro which might affect ganglioside signalling in higher organisms.http://dx.doi.org/10.1155/2018/3845027 |