Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow
The cytotoxicity of quercetin is not well understood. Using an ICR murine model, we unexpectedly found that mice exposed to 7 Gy total body irradiation (TBI) exhibited general in vivo toxicity after receiving quercetin (100 mg/kg PO), whereas this result was not observed in mice that received TBI on...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750014000596 |
| _version_ | 1818887867925004288 |
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| author | Ruiqing Chen Jingan Lin Jingshen Hong Deping Han Addison D. Zhang Ruilong Lan Lengxi Fu Zhaoyang Wu Jianhua Lin Weijian Zhang Zeng Wang Wei Chen Chun Chen Hengshan Zhang |
| author_facet | Ruiqing Chen Jingan Lin Jingshen Hong Deping Han Addison D. Zhang Ruilong Lan Lengxi Fu Zhaoyang Wu Jianhua Lin Weijian Zhang Zeng Wang Wei Chen Chun Chen Hengshan Zhang |
| author_sort | Ruiqing Chen |
| collection | DOAJ |
| description | The cytotoxicity of quercetin is not well understood. Using an ICR murine model, we unexpectedly found that mice exposed to 7 Gy total body irradiation (TBI) exhibited general in vivo toxicity after receiving quercetin (100 mg/kg PO), whereas this result was not observed in mice that received TBI only. In order to understand the involvement of alterations in mitochondrial biogenesis, we used a real-time qPCR to analyze the mitochondrial DNA copy number (mtDNAcn) by amplifying the MTRNR1 (12S rRNA) gene in murine bone marrow. We also utilized reverse transcription qPCR to determine the mRNA amounts transcribed from the polymerase gamma (POLG), POLG2, and mammalian mitochondrial transcription factor A (TFAM) genes in the tissue. In the mice exposed to TBI combined with quercetin, we found: (1) the radiation-induced increase of mtDNAcn was inhibited with a concurrent significant decrease in POLG expression; (2) TFAM expression was significantly increased; and (3) the expression of POLG2 was not influenced by the treatments. These data suggest that the overall toxicity was in part associated with the decrease in mtDNAcn, an effect apparently caused by the inhibition of POLG expression and overexpression of TFAM; unaltered POLG2 expression did not seem to contribute to toxicity. |
| first_indexed | 2024-12-19T16:44:04Z |
| format | Article |
| id | doaj.art-7713f2fabbb94030b267b3c81b661042 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-12-19T16:44:04Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-7713f2fabbb94030b267b3c81b6610422022-12-21T20:13:42ZengElsevierToxicology Reports2214-75002014-01-011C45045810.1016/j.toxrep.2014.07.014Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrowRuiqing Chen0Jingan Lin1Jingshen Hong2Deping Han3Addison D. Zhang4Ruilong Lan5Lengxi Fu6Zhaoyang Wu7Jianhua Lin8Weijian Zhang9Zeng Wang10Wei Chen11Chun Chen12Hengshan Zhang13Central Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaDepartment of Orthopedics, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaCentral Laboratory, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaThe cytotoxicity of quercetin is not well understood. Using an ICR murine model, we unexpectedly found that mice exposed to 7 Gy total body irradiation (TBI) exhibited general in vivo toxicity after receiving quercetin (100 mg/kg PO), whereas this result was not observed in mice that received TBI only. In order to understand the involvement of alterations in mitochondrial biogenesis, we used a real-time qPCR to analyze the mitochondrial DNA copy number (mtDNAcn) by amplifying the MTRNR1 (12S rRNA) gene in murine bone marrow. We also utilized reverse transcription qPCR to determine the mRNA amounts transcribed from the polymerase gamma (POLG), POLG2, and mammalian mitochondrial transcription factor A (TFAM) genes in the tissue. In the mice exposed to TBI combined with quercetin, we found: (1) the radiation-induced increase of mtDNAcn was inhibited with a concurrent significant decrease in POLG expression; (2) TFAM expression was significantly increased; and (3) the expression of POLG2 was not influenced by the treatments. These data suggest that the overall toxicity was in part associated with the decrease in mtDNAcn, an effect apparently caused by the inhibition of POLG expression and overexpression of TFAM; unaltered POLG2 expression did not seem to contribute to toxicity.http://www.sciencedirect.com/science/article/pii/S2214750014000596QuercetinRadiationMitochondrial DNA copy numberPOLGPOLG2TFAM |
| spellingShingle | Ruiqing Chen Jingan Lin Jingshen Hong Deping Han Addison D. Zhang Ruilong Lan Lengxi Fu Zhaoyang Wu Jianhua Lin Weijian Zhang Zeng Wang Wei Chen Chun Chen Hengshan Zhang Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow Toxicology Reports Quercetin Radiation Mitochondrial DNA copy number POLG POLG2 TFAM |
| title | Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow |
| title_full | Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow |
| title_fullStr | Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow |
| title_full_unstemmed | Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow |
| title_short | Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow |
| title_sort | potential toxicity of quercetin the repression of mitochondrial copy number via decreased polg expression and excessive tfam expression in irradiated murine bone marrow |
| topic | Quercetin Radiation Mitochondrial DNA copy number POLG POLG2 TFAM |
| url | http://www.sciencedirect.com/science/article/pii/S2214750014000596 |
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