Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edema
Objective To investigate the mechanism through which mtDNA3010 genotype variation leads to high-altitude pulmonary edema. Methods We assessed the functional impact of mtDNA3100 A/G genotype variation while maintaining C genotypes at the sites of mtDNA5178 and mtDNA10400. Two haplotype fusion cell mo...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | zho |
| Published: |
Editorial Office of Journal of Third Military Medical University
2019-04-01
|
| Series: | Di-san junyi daxue xuebao |
| Subjects: | |
| Online Access: | http://aammt.tmmu.edu.cn/Upload/rhtml/201812008.htm |
| _version_ | 1818885895483293696 |
|---|---|
| author | CHEN Yu GONG Liang CHEN Xingshu WANG Rui LUO Yongjun |
| author_facet | CHEN Yu GONG Liang CHEN Xingshu WANG Rui LUO Yongjun |
| author_sort | CHEN Yu |
| collection | DOAJ |
| description | Objective To investigate the mechanism through which mtDNA3010 genotype variation leads to high-altitude pulmonary edema. Methods We assessed the functional impact of mtDNA3100 A/G genotype variation while maintaining C genotypes at the sites of mtDNA5178 and mtDNA10400. Two haplotype fusion cell models with genotype combinations at mtDNA3010, 5178 and 10400 of A-C-C and G-C-C were established using mitochondrial DNA-depleted ρ0206 cells. The 2 fusion cell models were exposed to 1% O2 for 24 h, and the production of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of the cells were detected with flow cytometry. The content of ATP was detected using a chemiluminescence method, and the expression levels of voltage-dependent anion channel1 (VDAC1) and Bax proteins were detected using Western blotting. Quantitative RT-PCR was employed to determine the mitochondrial copy number and the expression of ERK, JNK, TFAM, ATP5A1 and ATP5I. Results In mt3010A and mt3010G fusion cells, the exposure to 1% O2 for 24 h did not produce significant differences in the fluorescence intensity of ROS, MMP, ATP content, mitochondrial DNA copy number, or the relative protein expression levels of VDAC1 and Bax (all P>0.05).The expression levels of ERK, JNK, TFAM, ATP5A1 and ATP5I genes were significantly higher in mtDNA3010A fusion cells than those in mtDNA3010G fusion cells after the hypoxic exposure (P < 0.05). Conclusion mtDNA3010A/G variation can affect energy metabolism of the mitochondria, and the disturbance in energy metabolism may contribute to the pathogenesis of high-altitude pulmonary edema. |
| first_indexed | 2024-12-19T16:12:42Z |
| format | Article |
| id | doaj.art-ada5f7b56cc54138857c63b2c98f4b02 |
| institution | Directory Open Access Journal |
| issn | 1000-5404 |
| language | zho |
| last_indexed | 2024-12-19T16:12:42Z |
| publishDate | 2019-04-01 |
| publisher | Editorial Office of Journal of Third Military Medical University |
| record_format | Article |
| series | Di-san junyi daxue xuebao |
| spelling | doaj.art-ada5f7b56cc54138857c63b2c98f4b022022-12-21T20:14:43ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042019-04-0141873474010.16016/j.1000-5404.201812008Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edemaCHEN Yu0GONG Liang1CHEN Xingshu2WANG Rui3LUO Yongjun4Development, Army Health Service Training Base, Army Medical University (Third Military Medical University), Chongqing, 400038, China Development, Army Health Service Training Base, Army Medical University (Third Military Medical University), Chongqing, 400038, China Development, Army Health Service Training Base, Army Medical University (Third Military Medical University), Chongqing, 400038, China Development, Army Health Service Training Base, Army Medical University (Third Military Medical University), Chongqing, 400038, China Development, Army Health Service Training Base, Army Medical University (Third Military Medical University), Chongqing, 400038, China Objective To investigate the mechanism through which mtDNA3010 genotype variation leads to high-altitude pulmonary edema. Methods We assessed the functional impact of mtDNA3100 A/G genotype variation while maintaining C genotypes at the sites of mtDNA5178 and mtDNA10400. Two haplotype fusion cell models with genotype combinations at mtDNA3010, 5178 and 10400 of A-C-C and G-C-C were established using mitochondrial DNA-depleted ρ0206 cells. The 2 fusion cell models were exposed to 1% O2 for 24 h, and the production of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of the cells were detected with flow cytometry. The content of ATP was detected using a chemiluminescence method, and the expression levels of voltage-dependent anion channel1 (VDAC1) and Bax proteins were detected using Western blotting. Quantitative RT-PCR was employed to determine the mitochondrial copy number and the expression of ERK, JNK, TFAM, ATP5A1 and ATP5I. Results In mt3010A and mt3010G fusion cells, the exposure to 1% O2 for 24 h did not produce significant differences in the fluorescence intensity of ROS, MMP, ATP content, mitochondrial DNA copy number, or the relative protein expression levels of VDAC1 and Bax (all P>0.05).The expression levels of ERK, JNK, TFAM, ATP5A1 and ATP5I genes were significantly higher in mtDNA3010A fusion cells than those in mtDNA3010G fusion cells after the hypoxic exposure (P < 0.05). Conclusion mtDNA3010A/G variation can affect energy metabolism of the mitochondria, and the disturbance in energy metabolism may contribute to the pathogenesis of high-altitude pulmonary edema.http://aammt.tmmu.edu.cn/Upload/rhtml/201812008.htmmitochondrial dnavariationenergy metabolismhigh-altitude pulmonary edema |
| spellingShingle | CHEN Yu GONG Liang CHEN Xingshu WANG Rui LUO Yongjun Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edema Di-san junyi daxue xuebao mitochondrial dna variation energy metabolism high-altitude pulmonary edema |
| title | Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edema |
| title_full | Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edema |
| title_fullStr | Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edema |
| title_full_unstemmed | Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edema |
| title_short | Role of mtDNA3010 A/G genotype variation in pathogenesis of high-altitude pulmonary edema |
| title_sort | role of mtdna3010 a g genotype variation in pathogenesis of high altitude pulmonary edema |
| topic | mitochondrial dna variation energy metabolism high-altitude pulmonary edema |
| url | http://aammt.tmmu.edu.cn/Upload/rhtml/201812008.htm |
| work_keys_str_mv | AT chenyu roleofmtdna3010aggenotypevariationinpathogenesisofhighaltitudepulmonaryedema AT gongliang roleofmtdna3010aggenotypevariationinpathogenesisofhighaltitudepulmonaryedema AT chenxingshu roleofmtdna3010aggenotypevariationinpathogenesisofhighaltitudepulmonaryedema AT wangrui roleofmtdna3010aggenotypevariationinpathogenesisofhighaltitudepulmonaryedema AT luoyongjun roleofmtdna3010aggenotypevariationinpathogenesisofhighaltitudepulmonaryedema |