Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.

<h4>Background</h4>Viral transformation of a cell starts at the genetic level, followed by changes in the proteome and the metabolome of the host. There is limited information on the broad metabolic changes in HTLV transformed cells.<h4>Methods and principal findings</h4>Here...

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Autores principales:	Prabhakar Sripadi, Bindesh Shrestha, Rebecca L Easley, Lawrence Carpio, Kylene Kehn-Hall, Sebastien Chevalier, Renaud Mahieux, Fatah Kashanchi, Akos Vertes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12edf388ec634660ae6773106a1bab6b
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spelling	oai:doaj.org-article:12edf388ec634660ae6773106a1bab6b2021-11-18T06:35:22ZDirect detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.1932-620310.1371/journal.pone.0012590https://doaj.org/article/12edf388ec634660ae6773106a1bab6b2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20830293/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Viral transformation of a cell starts at the genetic level, followed by changes in the proteome and the metabolome of the host. There is limited information on the broad metabolic changes in HTLV transformed cells.<h4>Methods and principal findings</h4>Here, we report the detection of key changes in metabolites and lipids directly from human T-lymphotropic virus type 1 and type 3 (HTLV1 and HTLV3) transformed, as well as Tax1 and Tax3 expressing cell lines by laser ablation electrospray ionization (LAESI) mass spectrometry (MS). Comparing LAESI-MS spectra of non-HTLV1 transformed and HTLV1 transformed cells revealed that glycerophosphocholine (PC) lipid components were dominant in the non-HTLV1 transformed cells, and PC(O-32:1) and PC(O-34:1) plasmalogens were displaced by PC(30:0) and PC(32:0) species in the HTLV1 transformed cells. In HTLV1 transformed cells, choline, phosphocholine, spermine and glutathione, among others, were downregulated, whereas creatine, dopamine, arginine and AMP were present at higher levels. When comparing metabolite levels between HTLV3 and Tax3 transfected 293T cells, there were a number of common changes observed, including decreased choline, phosphocholine, spermine, homovanillic acid, and glycerophosphocholine and increased spermidine and N-acetyl aspartic acid. These results indicate that the lipid metabolism pathway as well as the creatine and polyamine biosynthesis pathways are commonly deregulated after expression of HTLV3 and Tax3, indicating that the noted changes are likely due to Tax3 expression. N-acetyl aspartic acid is a novel metabolite that is upregulated in all cell types and all conditions tested.<h4>Conclusions and significance</h4>We demonstrate the high throughput in situ metabolite profiling of HTLV transformed and Tax expressing cells, which facilitates the identification of virus-induced perturbations in the biochemical processes of the host cells. We found virus type-specific (HTLV1 vs. HTLV3), expression-specific (Tax1 vs. Tax3) and cell-type-specific (T lymphocytes vs. kidney epithelial cells) changes in the metabolite profiles. The new insight on the affected metabolic pathways can be used to better understand the molecular mechanisms of HTLV induced transformation, which in turn can result in new treatment strategies.Prabhakar SripadiBindesh ShresthaRebecca L EasleyLawrence CarpioKylene Kehn-HallSebastien ChevalierRenaud MahieuxFatah KashanchiAkos VertesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9, p e12590 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Prabhakar Sripadi Bindesh Shrestha Rebecca L Easley Lawrence Carpio Kylene Kehn-Hall Sebastien Chevalier Renaud Mahieux Fatah Kashanchi Akos Vertes Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.
description	<h4>Background</h4>Viral transformation of a cell starts at the genetic level, followed by changes in the proteome and the metabolome of the host. There is limited information on the broad metabolic changes in HTLV transformed cells.<h4>Methods and principal findings</h4>Here, we report the detection of key changes in metabolites and lipids directly from human T-lymphotropic virus type 1 and type 3 (HTLV1 and HTLV3) transformed, as well as Tax1 and Tax3 expressing cell lines by laser ablation electrospray ionization (LAESI) mass spectrometry (MS). Comparing LAESI-MS spectra of non-HTLV1 transformed and HTLV1 transformed cells revealed that glycerophosphocholine (PC) lipid components were dominant in the non-HTLV1 transformed cells, and PC(O-32:1) and PC(O-34:1) plasmalogens were displaced by PC(30:0) and PC(32:0) species in the HTLV1 transformed cells. In HTLV1 transformed cells, choline, phosphocholine, spermine and glutathione, among others, were downregulated, whereas creatine, dopamine, arginine and AMP were present at higher levels. When comparing metabolite levels between HTLV3 and Tax3 transfected 293T cells, there were a number of common changes observed, including decreased choline, phosphocholine, spermine, homovanillic acid, and glycerophosphocholine and increased spermidine and N-acetyl aspartic acid. These results indicate that the lipid metabolism pathway as well as the creatine and polyamine biosynthesis pathways are commonly deregulated after expression of HTLV3 and Tax3, indicating that the noted changes are likely due to Tax3 expression. N-acetyl aspartic acid is a novel metabolite that is upregulated in all cell types and all conditions tested.<h4>Conclusions and significance</h4>We demonstrate the high throughput in situ metabolite profiling of HTLV transformed and Tax expressing cells, which facilitates the identification of virus-induced perturbations in the biochemical processes of the host cells. We found virus type-specific (HTLV1 vs. HTLV3), expression-specific (Tax1 vs. Tax3) and cell-type-specific (T lymphocytes vs. kidney epithelial cells) changes in the metabolite profiles. The new insight on the affected metabolic pathways can be used to better understand the molecular mechanisms of HTLV induced transformation, which in turn can result in new treatment strategies.
format	article
author	Prabhakar Sripadi Bindesh Shrestha Rebecca L Easley Lawrence Carpio Kylene Kehn-Hall Sebastien Chevalier Renaud Mahieux Fatah Kashanchi Akos Vertes
author_facet	Prabhakar Sripadi Bindesh Shrestha Rebecca L Easley Lawrence Carpio Kylene Kehn-Hall Sebastien Chevalier Renaud Mahieux Fatah Kashanchi Akos Vertes
author_sort	Prabhakar Sripadi
title	Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.
title_short	Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.
title_full	Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.
title_fullStr	Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.
title_full_unstemmed	Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.
title_sort	direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/12edf388ec634660ae6773106a1bab6b
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Direct detection of diverse metabolic changes in virally transformed and tax-expressing cells by mass spectrometry.

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