Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.

Thallium (Tl) is a heavy metal with toxicity comparative to other heavy metals such as As, Cd, and Hg. Nevertheless, fewer studies have been reported concerning the molecular mechanism of Tl toxicity as compared to other heavy metals. To obtain insight into Tl toxicity in the kidney, rats were intra...

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Main Authors: Sho Sugahara, Kana Unuma, Shuheng Wen, Takeshi Funakoshi, Toshihiko Aki, Koichi Uemura
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0311884&type=printable
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author Sho Sugahara
Kana Unuma
Shuheng Wen
Takeshi Funakoshi
Toshihiko Aki
Koichi Uemura
author_facet Sho Sugahara
Kana Unuma
Shuheng Wen
Takeshi Funakoshi
Toshihiko Aki
Koichi Uemura
author_sort Sho Sugahara
collection DOAJ
description Thallium (Tl) is a heavy metal with toxicity comparative to other heavy metals such as As, Cd, and Hg. Nevertheless, fewer studies have been reported concerning the molecular mechanism of Tl toxicity as compared to other heavy metals. To obtain insight into Tl toxicity in the kidney, rats were intraperitoneally administered Tl2SO4 (30 mg/kg), and the kidneys were removed 2 or 5 days later to examine the effects of Tl. Transcriptome analysis using DNA microarray of the rat kidney 2 and 5 days after Tl administration showed that cytoplasmic ribosomal proteins are the most upregulated category; many of the genes involved in ribosome biosynthesis were upregulated by Tl administration. This upregulation was associated with the activation of eukaryotic transcription initiation factor 2α (eIF2α), implying that increased ribosome biogenesis was linked to the subsequent activation of protein translation. In contrast, decreased mitochondrial biogenesis was revealed via proteomic analysis. Although we found an increase in Myc, a positive regulator of both ribosomal and mitochondrial biogenesis, decreased levels of NRF1 and TFAM, positive regulators of mitochondrial biogenesis whose gene expression is directory activated by Myc, were paradoxically observed. Taken together, differing responses of ribosomes and mitochondria to Tl toxicity were observed. Failure of transmission of the Myc signal to NRF1/TFAM might be involved in the observed disruption of coordinated responses in mitochondria and ribosomes during Tl administration in rat kidney.
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spelling doaj-art-99331e575cb24e81ba096e6466d9735b2024-12-10T05:32:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031188410.1371/journal.pone.0311884Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.Sho SugaharaKana UnumaShuheng WenTakeshi FunakoshiToshihiko AkiKoichi UemuraThallium (Tl) is a heavy metal with toxicity comparative to other heavy metals such as As, Cd, and Hg. Nevertheless, fewer studies have been reported concerning the molecular mechanism of Tl toxicity as compared to other heavy metals. To obtain insight into Tl toxicity in the kidney, rats were intraperitoneally administered Tl2SO4 (30 mg/kg), and the kidneys were removed 2 or 5 days later to examine the effects of Tl. Transcriptome analysis using DNA microarray of the rat kidney 2 and 5 days after Tl administration showed that cytoplasmic ribosomal proteins are the most upregulated category; many of the genes involved in ribosome biosynthesis were upregulated by Tl administration. This upregulation was associated with the activation of eukaryotic transcription initiation factor 2α (eIF2α), implying that increased ribosome biogenesis was linked to the subsequent activation of protein translation. In contrast, decreased mitochondrial biogenesis was revealed via proteomic analysis. Although we found an increase in Myc, a positive regulator of both ribosomal and mitochondrial biogenesis, decreased levels of NRF1 and TFAM, positive regulators of mitochondrial biogenesis whose gene expression is directory activated by Myc, were paradoxically observed. Taken together, differing responses of ribosomes and mitochondria to Tl toxicity were observed. Failure of transmission of the Myc signal to NRF1/TFAM might be involved in the observed disruption of coordinated responses in mitochondria and ribosomes during Tl administration in rat kidney.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0311884&type=printable
spellingShingle Sho Sugahara
Kana Unuma
Shuheng Wen
Takeshi Funakoshi
Toshihiko Aki
Koichi Uemura
Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.
PLoS ONE
title Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.
title_full Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.
title_fullStr Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.
title_full_unstemmed Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.
title_short Dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney.
title_sort dissociation of mitochondrial and ribosomal biogenesis during thallium administration in rat kidney
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0311884&type=printable
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AT takeshifunakoshi dissociationofmitochondrialandribosomalbiogenesisduringthalliumadministrationinratkidney
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