Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.

<h4>Background</h4>Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I ex...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Malin Larsson, Nils Rudqvist, Johan Spetz, Emman Shubbar, Toshima Z Parris, Britta Langen, Khalil Helou, Eva Forssell-Aronsson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/691608dc95d84e2f98dbb8ed6e2d3170
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:691608dc95d84e2f98dbb8ed6e2d3170
record_format	dspace
spelling	oai:doaj.org-article:691608dc95d84e2f98dbb8ed6e2d31702021-12-02T20:04:09ZLong-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.1932-620310.1371/journal.pone.0244098https://doaj.org/article/691608dc95d84e2f98dbb8ed6e2d31702020-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0244098https://doaj.org/toc/1932-6203<h4>Background</h4>Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I exposure is of great clinical and radiation protection interest. The aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats and identify potential biomarkers.<h4>Materials and methods</h4>Male Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1-1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression profiles in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). The gene expression microarray data and LC-MS/MS data were validated using qRT-PCR and ELISA, respectively.<h4>Results</h4>Nine 131I exposure-related candidate biomarkers (transcripts: Afp and RT1-Bb, and proteins: ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Two dose-related protein candidate biomarkers were identified in thyroid (APRT and LDHA) and two in plasma (DSG4 and TGM3). Candidate biomarkers for thyroid function included the ACADL and SORBS2 (all activities), TPO and TG proteins (low activities). 131I exposure was shown to have a profound effect on metabolism, immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated.<h4>Conclusion</h4>Exposure-related and dose-related effects on gene and protein expression generated few expression patterns useful as biomarkers for thyroid function and cancer.Malin LarssonNils RudqvistJohan SpetzEmman ShubbarToshima Z ParrisBritta LangenKhalil HelouEva Forssell-AronssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 15, Iss 12, p e0244098 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Malin Larsson Nils Rudqvist Johan Spetz Emman Shubbar Toshima Z Parris Britta Langen Khalil Helou Eva Forssell-Aronsson Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
description	<h4>Background</h4>Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I exposure is of great clinical and radiation protection interest. The aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats and identify potential biomarkers.<h4>Materials and methods</h4>Male Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1-1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression profiles in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). The gene expression microarray data and LC-MS/MS data were validated using qRT-PCR and ELISA, respectively.<h4>Results</h4>Nine 131I exposure-related candidate biomarkers (transcripts: Afp and RT1-Bb, and proteins: ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Two dose-related protein candidate biomarkers were identified in thyroid (APRT and LDHA) and two in plasma (DSG4 and TGM3). Candidate biomarkers for thyroid function included the ACADL and SORBS2 (all activities), TPO and TG proteins (low activities). 131I exposure was shown to have a profound effect on metabolism, immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated.<h4>Conclusion</h4>Exposure-related and dose-related effects on gene and protein expression generated few expression patterns useful as biomarkers for thyroid function and cancer.
format	article
author	Malin Larsson Nils Rudqvist Johan Spetz Emman Shubbar Toshima Z Parris Britta Langen Khalil Helou Eva Forssell-Aronsson
author_facet	Malin Larsson Nils Rudqvist Johan Spetz Emman Shubbar Toshima Z Parris Britta Langen Khalil Helou Eva Forssell-Aronsson
author_sort	Malin Larsson
title	Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
title_short	Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
title_full	Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
title_fullStr	Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
title_full_unstemmed	Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
title_sort	long-term transcriptomic and proteomic effects in sprague dawley rat thyroid and plasma after internal low dose 131i exposure.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/691608dc95d84e2f98dbb8ed6e2d3170
work_keys_str_mv	AT malinlarsson longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure AT nilsrudqvist longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure AT johanspetz longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure AT emmanshubbar longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure AT toshimazparris longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure AT brittalangen longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure AT khalilhelou longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure AT evaforssellaronsson longtermtranscriptomicandproteomiceffectsinspraguedawleyratthyroidandplasmaafterinternallowdose131iexposure
_version_	1718375607207723008

Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.

Ejemplares similares