Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.

The glycolipid transfer protein (GLTP) catalyzes the binding and transport of glycolipids, but not phospholipids or neutral lipids. With its all-alpha helical fold, it is the founding member for a new superfamily, however its biological role still remains unclear. We have analyzed changes in the HeL...

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Autores principales:	Matti A Kjellberg, Anders P E Backman, Henna Ohvo-Rekilä, Peter Mattjus
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0f473adf22944d68491b5a42c72299f
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spelling	oai:doaj.org-article:f0f473adf22944d68491b5a42c72299f2021-11-18T08:19:32ZAlternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.1932-620310.1371/journal.pone.0097263https://doaj.org/article/f0f473adf22944d68491b5a42c72299f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24824606/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The glycolipid transfer protein (GLTP) catalyzes the binding and transport of glycolipids, but not phospholipids or neutral lipids. With its all-alpha helical fold, it is the founding member for a new superfamily, however its biological role still remains unclear. We have analyzed changes in the HeLa cell lipidome in response to down- and up-regulation of GLTP expression. We used metabolic labeling and thin layer chromatography analysis, complemented with a lipidomics mass spectroscopic approach. HeLa cells were treated with GLTP siRNA or were transiently overexpressing the GLTP gene. We identified eight different lipid classes that changed as a result of the GLTP down- or up-regulation treatments; glucosylceramide, lactosylceramide, globotriaosylceramide, ceramide, sphingomyelin, cholesterol-esters, diacylglycerol and phosphatidylserine. We discovered that the amount of globotriaosylceramide (Gb3) was extensively lowered after down-regulation of GLTP. Further, an up-regulation of GLTP caused a substantial increase in both the Gb3 and glucosylceramide levels compared to the controls. Total galactosylceramide levels remained unchanged. Both lactosylceramide and ceramide showed small changes, an increase with increasing GLTP and a decrease in the HeLa cell GLTP knockdowns. The cholesterol-esters and diacylglycerol masses increased in cells that had upregulated GLTP protein levels, wheras down-regulation did not affect their amounts. For the glycerophospholipids, phosphatidylserine was the only species that was lower in GLTP overexpressing cells. Phosphatidylethanolamine, phosphatidylglyerol and phosphatidylinositol remained unaltered. A total of 142 lipid species were profiled and quantified using shotgun lipidomics analyses. This work provides for the first time insights into how alternations in the levels of a protein that binds and transfers glycolipids affects the cellular lipid metabolism. We discuss the observed changes in the lipidome and how these relate to GLTP. We suggest, that GLTP not only could be a significant player in cellular sphingolipid metabolism, but also could have a much broader role in the overall lipid metabolism.Matti A KjellbergAnders P E BackmanHenna Ohvo-RekiläPeter MattjusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97263 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matti A Kjellberg Anders P E Backman Henna Ohvo-Rekilä Peter Mattjus Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.
description	The glycolipid transfer protein (GLTP) catalyzes the binding and transport of glycolipids, but not phospholipids or neutral lipids. With its all-alpha helical fold, it is the founding member for a new superfamily, however its biological role still remains unclear. We have analyzed changes in the HeLa cell lipidome in response to down- and up-regulation of GLTP expression. We used metabolic labeling and thin layer chromatography analysis, complemented with a lipidomics mass spectroscopic approach. HeLa cells were treated with GLTP siRNA or were transiently overexpressing the GLTP gene. We identified eight different lipid classes that changed as a result of the GLTP down- or up-regulation treatments; glucosylceramide, lactosylceramide, globotriaosylceramide, ceramide, sphingomyelin, cholesterol-esters, diacylglycerol and phosphatidylserine. We discovered that the amount of globotriaosylceramide (Gb3) was extensively lowered after down-regulation of GLTP. Further, an up-regulation of GLTP caused a substantial increase in both the Gb3 and glucosylceramide levels compared to the controls. Total galactosylceramide levels remained unchanged. Both lactosylceramide and ceramide showed small changes, an increase with increasing GLTP and a decrease in the HeLa cell GLTP knockdowns. The cholesterol-esters and diacylglycerol masses increased in cells that had upregulated GLTP protein levels, wheras down-regulation did not affect their amounts. For the glycerophospholipids, phosphatidylserine was the only species that was lower in GLTP overexpressing cells. Phosphatidylethanolamine, phosphatidylglyerol and phosphatidylinositol remained unaltered. A total of 142 lipid species were profiled and quantified using shotgun lipidomics analyses. This work provides for the first time insights into how alternations in the levels of a protein that binds and transfers glycolipids affects the cellular lipid metabolism. We discuss the observed changes in the lipidome and how these relate to GLTP. We suggest, that GLTP not only could be a significant player in cellular sphingolipid metabolism, but also could have a much broader role in the overall lipid metabolism.
format	article
author	Matti A Kjellberg Anders P E Backman Henna Ohvo-Rekilä Peter Mattjus
author_facet	Matti A Kjellberg Anders P E Backman Henna Ohvo-Rekilä Peter Mattjus
author_sort	Matti A Kjellberg
title	Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.
title_short	Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.
title_full	Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.
title_fullStr	Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.
title_full_unstemmed	Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.
title_sort	alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f0f473adf22944d68491b5a42c72299f
work_keys_str_mv	AT mattiakjellberg alternationintheglycolipidtransferproteinexpressioncauseschangesinthecellularlipidome AT anderspebackman alternationintheglycolipidtransferproteinexpressioncauseschangesinthecellularlipidome AT hennaohvorekila alternationintheglycolipidtransferproteinexpressioncauseschangesinthecellularlipidome AT petermattjus alternationintheglycolipidtransferproteinexpressioncauseschangesinthecellularlipidome
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Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.

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