Proteomic analysis of mouse thymoma EL4 cells treated with bis(tri-<i>n</i>-butyltin)oxide (TBTO)

Osman, Ahmed; Kol, Sandra W. M. van; Peijnenburg, Ad; Blokland, Marco; Pennings, Jeroen L. A.; Kleinjans, J.C.S.; Loveren, Henk Van

doi:10.1080/15476910903051723

Cited by 16 publications

(8 citation statements)

References 70 publications

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“…The relative abundance of the identified proteins was estimated using observed peptide hits. This quantitative approach was successfully employed earlier for biomarker discovery in urine (Pang et al, 2002), for estimating changes in protein expression levels in yeast in function of carbon source (Gao et al, 2003) and, recently, we have applied it in evaluating protein expression changes of thymoma EL4 cells exposed to bis-(trin-butytin)oxide (TBTO) (Osman et al, 2009). In the present study, the expression levels of 30 proteins were affected.…”

Section: Introductionmentioning

confidence: 79%

Protein expression profiling of mouse thymoma cells upon exposure to the trichothecene deoxynivalenol (DON): Implications for its mechanism of action

Osman

Pennings

Blokland

et al. 2009

Journal of Immunotoxicology

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Section: Introductionmentioning

confidence: 79%

Protein expression profiling of mouse thymoma cells upon exposure to the trichothecene deoxynivalenol (DON): Implications for its mechanism of action

Osman

Pennings

Blokland

et al. 2009

Journal of Immunotoxicology

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“…EL4 cells were cultured as described previously (Osman et al ., ). Each treated sample or control contained c .…”

Section: Methodsmentioning

confidence: 97%

“…In an effort to understand the mechanism of action of TBTO at the molecular level, we undertook a proteomics study using the thymoma cell line (EL4), which has been used as a model for mouse thymus in mechanistic studies (El‐Darahali et al ., ; Lee et al ., ) possibly because of its possession of an immature thymus cell phenotype (Tanaka et al ., ). Earlier, we reported that TBTO affected 12 proteins including the downregulation of prothymosin alpha, a protein implicated in cell proliferation (Osman et al ., ). Recently, we reported the results of phosphoproteomic analysis of thymoma cells treated with TBTO (Osman and van Loveren, ), where we found that TBTO downregulated a number of phosphoproteins involved in cell proliferation and energy pathways.…”

Section: Introductionmentioning

confidence: 97%

The immunosuppressant tributyltin oxide blocks the mTOR pathway, like rapamycin, albeit by a different mechanism

Osman

Loveren

2013

J of Applied Toxicology

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We treated the thymoma cell line (EL4) with two model immunosuppressants, rapamycin and tributyltin oxide (TBTO), and compared their effects on the expression levels of proteins that are downstream targets of mTOR kinase 1 (mammalian target of rapamycin, known also as mechanistic target of rapamycin): p70 ribosomal S6 kinase1 and 4E-binding protein 1, a repressor of the cap-binding protein eIF4E. In addition, we evaluated the levels of ribosomal protein S6, p-eIF4B, substrates of p70S6 kinase1, matrin 3 and ribonucleotide reductase, subunit RRM2. The levels of these proteins were evaluated in cell lysates by immunoblot. We found that both compounds inhibited the phosphorylation state of p70S6 kinase 1 and its substrates; however, TBTO, in contrast to rapamycin, reduced the level of the total p70S6k1. Besides, we detected a band with a molecular weight of c. 32 kDa only in the TBTO-treated lysates. This band was detected with a monoclonal antibody specific for S6k1, suggesting that this band might be a degradation product of the kinase. Further, TBTO and rapamycin differentially affected 4E-binding protein 1; the former compound stimulated its phosphorylation state whereas the latter inhibited it. The two immunosuppressants did not affect the level of ribonucleotide reductase, but TBTO downregulated matrin3, in agreement with a previous report, whereas rapamycin had no effect on the expression level of this latter protein. We conclude that TBTO inhibits, like rapamycin, the p70 S6 kinase 1 pathway, but with a different mechanism. However, in contrast to rapamycin, which inhibits the cap-dependent translation, TBTO increases the phosphorylation of 4E-binding protein1.

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“…Recent study also shown that tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) have different effect on cell proliferation and expression of levels of apoptotic protein markers levels in human breast cancer MCF-7 cell line (Fickova et al 2015). In 2009, Osman et al reported proteomic profiling of mouse thymoma cells treated with tributyltin oxide and found that this compound altered the expression levels of 12 proteins, including prothymosin alpha (Osman et al 2009). Nevertheless, triorganotin-induced cytotoxicity involves different mechanisms of action depending on the compound, concentration, and incubation time (Ferreira et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Novel insights into the combined effect of triorganotin compounds and all-trans retinoic acid on expression of selected proteins associated with tumor progression in breast cancer cell line MDA-MB-231: Proteomic approach

Strouhalová

Toporová²,

Laštovičková³

et al. 2019

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Trialkyltins and triaryltins function as nuclear retinoid X receptors (RXR) agonists due to their affinity to the ligand-binding domain of RXR subtypes and function as transcriptional activators. We present the data on combined effects of all-trans retinoic acid (ATRA), retinoic acid receptor (RAR) ligand and tributyltin chloride or triphenyltin chloride (RXR ligands) on protein pattern in MDA-MB-231 cells. Proteomic strategies based on bottom-up method were applied in this study. The total cell proteins were extracted, separated on 2D SDS-PAGE and their characterization was achieved by MALDI-TOF/TOF MS/MS. By employing PDQuest™ software, we identified more than 30 proteins differently affected by the above compounds. For further studies, we selected specific proteins associated either with metabolic pathway (glyceraldehyde-3-phosphate dehydrogenase) or to cellular processes as apoptosis, regulation of gene transcription or epithelial-mesenchymal transition (annexin 5, nucleoside diphosphate kinase B and vimentin). We have found that treatment of MDA-MB-231 cells with triorganotins reduced the expression of studied proteins. Moreover, the treatment of MDA-MB-231 cells with triorganotin compounds together with ATRA resulted in an additional reduction of annexin 5, vimentin and nucleoside diphosphate kinase B. These results demonstrate that RXR/RAR heterodimer may act under this experimental design as permissive heterodimer allowing activation of RXR by triorganotins.

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Proteomic analysis of mouse thymoma EL4 cells treated with bis(tri-n-butyltin)oxide (TBTO)

Cited by 16 publications

References 70 publications

Protein expression profiling of mouse thymoma cells upon exposure to the trichothecene deoxynivalenol (DON): Implications for its mechanism of action

Protein expression profiling of mouse thymoma cells upon exposure to the trichothecene deoxynivalenol (DON): Implications for its mechanism of action

The immunosuppressant tributyltin oxide blocks the mTOR pathway, like rapamycin, albeit by a different mechanism

Novel insights into the combined effect of triorganotin compounds and all-trans retinoic acid on expression of selected proteins associated with tumor progression in breast cancer cell line MDA-MB-231: Proteomic approach

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