Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice
© 2018 The Author(s). Published by S. Karger AG, Basel..
BACKGROUND/AIMS: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells.
METHODS: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods.
RESULTS: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels.
CONCLUSION: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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| Enthalten in: |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology - 51(2018), 5 vom: 10., Seite 2421-2433 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Luo, Qin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.01.2019 Date Revised 12.02.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1159/000495899 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM291678734 |
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| 100 | 1 | |a Luo, Qin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice |
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| 500 | |a Date Revised 12.02.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 The Author(s). Published by S. Karger AG, Basel. | ||
| 520 | |a BACKGROUND/AIMS: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells | ||
| 520 | |a METHODS: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods | ||
| 520 | |a RESULTS: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels | ||
| 520 | |a CONCLUSION: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a G2/M phase arrest | |
| 650 | 4 | |a Kidney | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Proliferation | |
| 650 | 4 | |a Sodium fluoride | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 650 | 7 | |a Sodium Fluoride |2 NLM | |
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| 700 | 1 | |a Guo, Hongrui |e verfasserin |4 aut | |
| 700 | 1 | |a Kuang, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Hengmin |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Huidan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yujiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Linlin |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Zuo, Zhicai |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Junliang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yinglun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ling |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1159/000495899 |3 Volltext |
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