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A quantitative proteomics study for assessing rodent thyroid toxicity

ABSTRACT: Here, we aimed to use TMT based quantitative proteomics approach to investigate rodent thyroid toxicity. For this purpose, male Wistar rats have been exposed to a direct (6-propyl-2-thiouracil, PTU) and an indirect (phenytoin) thyroid toxicant, respectively. Thereby, two doses (high, low) and three treatment time points (short, long, and long+recovery) were investigated, allowing insights into the mode of actions during thyroid toxicity. Proteomics were applied to liver and thyroid tissues.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Liver, Thyroid Gland

SUBMITTER: Zhipeng Wang

LAB HEAD: Kristin Schubert

PROVIDER: PXD026835 | Pride | 2024-10-25

REPOSITORIES: Pride

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Source:

			Action	DRS
	Rattus-norvegicus_uniprot-proteome_reference_29944_20200803_ZW.fasta	Fasta
	XomeTox_L.mzML	Mzml
	XomeTox_L.mzid.gz	Mzid
	XomeTox_L_BP10_F1.raw	Raw
	XomeTox_L_BP10_F2.raw	Raw

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Project description:Background. Radioiodide 131I is commonly used to treat thyroid cancer and hyperthyroidism, and 131I releases during nuclear accidents have resulted in increased incidence of thyroid cancer in children. To develop a better understanding of underlying cellular mechanisms behind 131I exposure and identify potential biomarkers, 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. Materials and methods. 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 patterns in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). Results. Nine 131I exposure-related biomarkers (Afp and RT1-Bb,ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Four dose-related biomarker candidates (APRT, LDHA) and (TGM3 and DSG4) were identified in thyroid and plasma, respectively. Candidate biomarkers for thyroid function were the upstream regulator PPARG and the proteins ACADL and SORBS2 (all activities), TPO and TG (low activities)). 131I exposure was shown to have a profound effect on metabolism, the 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. Conclusion. Exposure-related and dose-related effects on gene and protein expression were observed, thereby identifying several candidate genes that could be used as potential biomarkers for exposure, absorbed dose and thyroid function.

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A quantitative proteomics study for assessing rodent thyroid toxicity

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