Vanadium Pentoxide Exposure Causes Strain-Dependent Changes in Mitochondrial DNA Heteroplasmy, Copy Number, and Lesions, but Not Nuclear DNA Lesions

被引：1

作者：

Dobson, Nick ^{[1
]}

Kleeberger, Steven ^{[2
]}

Burkholder, Adam ^{[2
]}

Walters, Dianne ^{[3
]}

Gladwell, Wesley ^{[2
]}

Gerrish, Kevin ^{[2
]}

Vellers, Heather ^{[4
]}

机构：

[1] Univ Oklahoma, Hlth & Exercise Dept, Norman, OK 73019 USA

[2] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA

[3] East Carolina Univ, Brody Sch Med, Dept Physiol, Greenville, NC 27834 USA

[4] Texas Tech Univ, Dept Kinesiol & Sport Management, Lubbock, TX 79409 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 19期

基金：

美国国家卫生研究院;

关键词：

mitochondrial sequencing; mtDNA copy number; mtDNA damage; heteroplasmy; vanadium pentoxide; DISEASES; DAMAGE; HEALTH; CELLS; MICE;

D O I：

10.3390/ijms241914507

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (V2O5) 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 V2O5-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-V2O5 exposure.

引用

页数：13