Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress
The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-04-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.00231/full |
| _version_ | 1819098715685650432 |
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| author | Nor Azian Abdul Murad Rahman Jamal Bee Hong Soon Bee Hong Soon Sue-Mian Then Sue-Mian Then Azizi Abu Bakar Farizal Fadzil Jegan Thanabalan Mohd S. Mohd Haspani Charng Jeng Toh Azmi Mohd Tamil Roslan Harun Wan Z. Wan Ngah |
| author_facet | Nor Azian Abdul Murad Rahman Jamal Bee Hong Soon Bee Hong Soon Sue-Mian Then Sue-Mian Then Azizi Abu Bakar Farizal Fadzil Jegan Thanabalan Mohd S. Mohd Haspani Charng Jeng Toh Azmi Mohd Tamil Roslan Harun Wan Z. Wan Ngah |
| author_sort | Nor Azian Abdul Murad |
| collection | DOAJ |
| description | The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress. |
| first_indexed | 2024-12-22T00:35:24Z |
| format | Article |
| id | doaj.art-972d915b101147d6833d5e0808040247 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-22T00:35:24Z |
| publishDate | 2017-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-972d915b101147d6833d5e08080402472022-12-21T18:44:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-04-01810.3389/fphys.2017.00231256088Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative StressNor Azian Abdul Murad0Rahman Jamal1Bee Hong Soon2Bee Hong Soon3Sue-Mian Then4Sue-Mian Then5Azizi Abu Bakar6Farizal Fadzil7Jegan Thanabalan8Mohd S. Mohd Haspani9Charng Jeng Toh10Azmi Mohd Tamil11Roslan Harun12Wan Z. Wan Ngah13UKM Medical Molecular Biology Institute, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaDivision of Neurosurgery, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaThe University of Nottingham Malaysia CampusSemenyih, MalaysiaDivision of Neurosurgery, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaDivision of Neurosurgery, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaDivision of Neurosurgery, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaNeurosurgery Department, Hospital Kuala LumpurKuala Lumpur, MalaysiaDivision of Neurosurgery, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaDepartment of Community Health, Faculty of Medicine, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaUKM Medical Molecular Biology Institute, Universiti Kebangsaan MalaysiaKuala Lumpur, MalaysiaThe role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.http://journal.frontiersin.org/article/10.3389/fphys.2017.00231/fullgliomasmitochondrial DNA mutationmitochondrial dysfunctionoxidative stress |
| spellingShingle | Nor Azian Abdul Murad Rahman Jamal Bee Hong Soon Bee Hong Soon Sue-Mian Then Sue-Mian Then Azizi Abu Bakar Farizal Fadzil Jegan Thanabalan Mohd S. Mohd Haspani Charng Jeng Toh Azmi Mohd Tamil Roslan Harun Wan Z. Wan Ngah Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress Frontiers in Physiology gliomas mitochondrial DNA mutation mitochondrial dysfunction oxidative stress |
| title | Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress |
| title_full | Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress |
| title_fullStr | Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress |
| title_full_unstemmed | Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress |
| title_short | Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress |
| title_sort | mitochondrial dna mutations in grade ii and iii glioma cell lines are associated with significant mitochondrial dysfunction and higher oxidative stress |
| topic | gliomas mitochondrial DNA mutation mitochondrial dysfunction oxidative stress |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.00231/full |
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