Thallium(I) treatment induces nucleolar stress to stop protein synthesis and cell growth
Identifieur interne : 000337 ( Pmc/Checkpoint ); précédent : 000336; suivant : 000338Thallium(I) treatment induces nucleolar stress to stop protein synthesis and cell growth
Auteurs : Yi-Ting Chou ; Kai-Yin LoSource :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
Thallium is considered as an emergent contaminant owing to its potential use in the superconductor alloys. The monovalent thallium, Tl(I), is highly toxic to the animals as it can affect numerous metabolic processes. Here we observed that Tl(I) decreased protein synthesis and phosphorylated eukaryotic initiation factor 2α. Although Tl(I) has been shown to interact with the sulfhydryl groups of proteins and cause the accumulation of reactive oxygen species, it did not activate endoplasmic reticulum stress. Notably, the level of 60S ribosomal subunit showed significant under-accumulation after the Tl(I) treatment. Given that Tl(I) shares similarities with potassium in terms of the ionic charge and atomic radius, we proposed that Tl(I) occupies certain K+-binding sites and inactivates the ribosomal function. However, we observed neither activation of ribophagy nor acceleration of the proteasomal degradation of 60S subunits. On the contrary, the ribosome synthesis pathway was severely blocked, i.e., the impairment of rRNA processing, deformed nucleoli, and accumulation of 60S subunits in the nucleus were observed. Although p53 remained inactivated, the decreased c-Myc and increased p21 levels indicated the activation of nucleolar stress. Therefore, we proposed that Tl(I) interfered the ribosome synthesis, thus resulting in cell growth inhibition and lethality.
Url:
DOI: 10.1038/s41598-019-43413-1
PubMed: 31061518
PubMed Central: 6502789
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<front><div type="abstract" xml:lang="en"><p id="Par1">Thallium is considered as an emergent contaminant owing to its potential use in the superconductor alloys. The monovalent thallium, Tl(I), is highly toxic to the animals as it can affect numerous metabolic processes. Here we observed that Tl(I) decreased protein synthesis and phosphorylated eukaryotic initiation factor 2α. Although Tl(I) has been shown to interact with the sulfhydryl groups of proteins and cause the accumulation of reactive oxygen species, it did not activate endoplasmic reticulum stress. Notably, the level of 60S ribosomal subunit showed significant under-accumulation after the Tl(I) treatment. Given that Tl(I) shares similarities with potassium in terms of the ionic charge and atomic radius, we proposed that Tl(I) occupies certain K<sup>+</sup>
-binding sites and inactivates the ribosomal function. However, we observed neither activation of ribophagy nor acceleration of the proteasomal degradation of 60S subunits. On the contrary, the ribosome synthesis pathway was severely blocked, i.e., the impairment of rRNA processing, deformed nucleoli, and accumulation of 60S subunits in the nucleus were observed. Although p53 remained inactivated, the decreased c-Myc and increased p21 levels indicated the activation of nucleolar stress. Therefore, we proposed that Tl(I) interfered the ribosome synthesis, thus resulting in cell growth inhibition and lethality.</p>
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<title-group><article-title>Thallium(I) treatment induces nucleolar stress to stop protein synthesis and cell growth</article-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Chou</surname>
<given-names>Yi-Ting</given-names>
</name>
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<name><surname>Lo</surname>
<given-names>Kai-Yin</given-names>
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<address><email>kaiyin@ntu.edu.tw</email>
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<aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0546 0241</institution-id>
<institution-id institution-id-type="GRID">grid.19188.39</institution-id>
<institution>Department of Agricultural Chemistry,</institution>
<institution>National Taiwan University,</institution>
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Taipei, Taiwan</aff>
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<pub-date pub-type="epub"><day>6</day>
<month>5</month>
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<history><date date-type="received"><day>21</day>
<month>9</month>
<year>2018</year>
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<date date-type="accepted"><day>17</day>
<month>12</month>
<year>2018</year>
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<permissions><copyright-statement>© The Author(s) 2019</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
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<abstract id="Abs1"><p id="Par1">Thallium is considered as an emergent contaminant owing to its potential use in the superconductor alloys. The monovalent thallium, Tl(I), is highly toxic to the animals as it can affect numerous metabolic processes. Here we observed that Tl(I) decreased protein synthesis and phosphorylated eukaryotic initiation factor 2α. Although Tl(I) has been shown to interact with the sulfhydryl groups of proteins and cause the accumulation of reactive oxygen species, it did not activate endoplasmic reticulum stress. Notably, the level of 60S ribosomal subunit showed significant under-accumulation after the Tl(I) treatment. Given that Tl(I) shares similarities with potassium in terms of the ionic charge and atomic radius, we proposed that Tl(I) occupies certain K<sup>+</sup>
-binding sites and inactivates the ribosomal function. However, we observed neither activation of ribophagy nor acceleration of the proteasomal degradation of 60S subunits. On the contrary, the ribosome synthesis pathway was severely blocked, i.e., the impairment of rRNA processing, deformed nucleoli, and accumulation of 60S subunits in the nucleus were observed. Although p53 remained inactivated, the decreased c-Myc and increased p21 levels indicated the activation of nucleolar stress. Therefore, we proposed that Tl(I) interfered the ribosome synthesis, thus resulting in cell growth inhibition and lethality.</p>
</abstract>
<kwd-group kwd-group-type="npg-subject"><title>Subject terms</title>
<kwd>Nucleolus</kwd>
<kwd>Ribosome</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100004663</institution-id>
<institution>Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)</institution>
</institution-wrap>
</funding-source>
<award-id>MOST 106-2313-B-002-031-MY3</award-id>
<award-id>MOST 106-2313-B-002-031-MY3</award-id>
<principal-award-recipient><name><surname>Chou</surname>
<given-names>Yi-Ting</given-names>
</name>
<name><surname>Lo</surname>
<given-names>Kai-Yin</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2019</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list></list>
<tree><noCountry><name sortKey="Chou, Yi Ting" sort="Chou, Yi Ting" uniqKey="Chou Y" first="Yi-Ting" last="Chou">Yi-Ting Chou</name>
<name sortKey="Lo, Kai Yin" sort="Lo, Kai Yin" uniqKey="Lo K" first="Kai-Yin" last="Lo">Kai-Yin Lo</name>
</noCountry>
</tree>
</affiliations>
</record>
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