Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions
Interstitial lung diseases (ILDs) are lethal lung diseases characterized by pulmonary inflammation and progressive lung interstitial scarring. We previously developed a mouse model of ILD using vanadium pentoxide (V<sub>2</sub>O<sub>5</sub>) and identified several gene candid...
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14507 |
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| author | Nick L. Dobson Steven R. Kleeberger Adam B. Burkholder Dianne M. Walters Wesley Gladwell Kevin Gerrish Heather L. Vellers |
| author_facet | Nick L. Dobson Steven R. Kleeberger Adam B. Burkholder Dianne M. Walters Wesley Gladwell Kevin Gerrish Heather L. Vellers |
| author_sort | Nick L. Dobson |
| collection | DOAJ |
| description | Interstitial lung diseases (ILDs) are lethal lung diseases characterized by pulmonary inflammation and progressive lung interstitial scarring. We previously developed a mouse model of ILD using vanadium pentoxide (V<sub>2</sub>O<sub>5</sub>) and identified several gene candidates on chromosome 4 associated with pulmonary fibrosis. While these data indicated a significant genetic contribution to ILD susceptibility, they did not include any potential associations and interactions with the mitochondrial genome that might influence disease risk. To conduct this pilot work, we selected the two divergent strains we previously categorized as V<sub>2</sub>O<sub>5</sub>-resistant C57BL6J (B6) and -responsive DBA/2J (D2) and compared their mitochondrial genome characteristics, including DNA variants, heteroplasmy, lesions, and copy numbers at 14- and 112-days post-exposure. While we did not find changes in the mitochondrial genome at 14 days post-exposure, at 112 days, we found that the responsive D2 strain exhibited significantly fewer mtDNA copies and more lesions than control animals. Alongside these findings, mtDNA heteroplasmy frequency decreased. These data suggest that mice previously shown to exhibit increased susceptibility to pulmonary fibrosis and inflammation sustain damage to the mitochondrial genome that is evident at 112 days post-V<sub>2</sub>O<sub>5</sub> exposure. |
| first_indexed | 2024-03-10T21:43:37Z |
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| id | doaj.art-5978b6b6717e4e70ae1de1288a5f6447 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:43:37Z |
| publishDate | 2023-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5978b6b6717e4e70ae1de1288a5f64472023-11-19T14:27:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191450710.3390/ijms241914507Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA LesionsNick L. Dobson0Steven R. Kleeberger1Adam B. Burkholder2Dianne M. Walters3Wesley Gladwell4Kevin Gerrish5Heather L. Vellers6Health and Exercise Department, University of Oklahoma, Norman, OK 73019, USANational Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USANational Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USADepartment of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USANational Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USANational Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USADepartment of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX 79409, USAInterstitial lung diseases (ILDs) are lethal lung diseases characterized by pulmonary inflammation and progressive lung interstitial scarring. We previously developed a mouse model of ILD using vanadium pentoxide (V<sub>2</sub>O<sub>5</sub>) and identified several gene candidates on chromosome 4 associated with pulmonary fibrosis. While these data indicated a significant genetic contribution to ILD susceptibility, they did not include any potential associations and interactions with the mitochondrial genome that might influence disease risk. To conduct this pilot work, we selected the two divergent strains we previously categorized as V<sub>2</sub>O<sub>5</sub>-resistant C57BL6J (B6) and -responsive DBA/2J (D2) and compared their mitochondrial genome characteristics, including DNA variants, heteroplasmy, lesions, and copy numbers at 14- and 112-days post-exposure. While we did not find changes in the mitochondrial genome at 14 days post-exposure, at 112 days, we found that the responsive D2 strain exhibited significantly fewer mtDNA copies and more lesions than control animals. Alongside these findings, mtDNA heteroplasmy frequency decreased. These data suggest that mice previously shown to exhibit increased susceptibility to pulmonary fibrosis and inflammation sustain damage to the mitochondrial genome that is evident at 112 days post-V<sub>2</sub>O<sub>5</sub> exposure.https://www.mdpi.com/1422-0067/24/19/14507mitochondrial sequencingmtDNA copy numbermtDNA damageheteroplasmyvanadium pentoxide |
| spellingShingle | Nick L. Dobson Steven R. Kleeberger Adam B. Burkholder Dianne M. Walters Wesley Gladwell Kevin Gerrish Heather L. Vellers Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions International Journal of Molecular Sciences mitochondrial sequencing mtDNA copy number mtDNA damage heteroplasmy vanadium pentoxide |
| title | Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions |
| title_full | Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions |
| title_fullStr | Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions |
| title_full_unstemmed | Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions |
| title_short | Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions |
| title_sort | vanadium pentoxide exposure causes strain dependent changes in mitochondrial dna heteroplasmy copy number and lesions but not nuclear dna lesions |
| topic | mitochondrial sequencing mtDNA copy number mtDNA damage heteroplasmy vanadium pentoxide |
| url | https://www.mdpi.com/1422-0067/24/19/14507 |
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