Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells
Periodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compa...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/2/226 |
| _version_ | 1797622738650660864 |
|---|---|
| author | Ildete L. Ferreira Solange Costa Bruno J. Moraes Ana Costa Olga Fokt Daniela Marinho Vera Alves Isabel P. Baptista A. Cristina Rego |
| author_facet | Ildete L. Ferreira Solange Costa Bruno J. Moraes Ana Costa Olga Fokt Daniela Marinho Vera Alves Isabel P. Baptista A. Cristina Rego |
| author_sort | Ildete L. Ferreira |
| collection | DOAJ |
| description | Periodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compared to PDT, T2D patients, and control individuals. PBMCs were analyzed for mitochondrial respiration, reactive oxygen species, antioxidant proteins, and expression of Nrf2-target genes. PDT and T2D-PDT patients exhibited altered periodontal clinical markers, while T2D and T2D-PDT patients displayed increased blood HbA1c. Decreased oxygen consumption and ATP production were observed in the PDT patient’s PBMCs. PDT and T2D-PDT PBMCs also evidenced increased H<sub>2</sub>O<sub>2</sub> levels and reduced catalase levels (also detected in T2D patients), whereas a compromised glutathione cycle was observed in T2D-PDT patients. PBMCs from both T2D or T2D-PDT patients showed increased Nrf2 protein levels, enhanced GCL activity and GCL-catalytic subunit protein levels, and maintained GCLc, GST, and HO-1 mRNA levels. In contrast, the expressions of Nrf2-target genes were significantly diminished in the PDT patient’s PBMCs. Decreased SOD1 and GST mRNA levels were also observed in CD3+CD8+-lymphocytes derived from PDT and T2D-PDT patients. In conclusion, PBMCs from T2D-PDT patients showed major redox changes, while mononuclear cells from PDT patients showed mitochondrial deregulation and reduced expression of Nrf2-target genes. |
| first_indexed | 2024-03-11T09:15:30Z |
| format | Article |
| id | doaj.art-eb8298447dd1411a83e3513f14260529 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:15:30Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-eb8298447dd1411a83e3513f142605292023-11-16T18:45:08ZengMDPI AGAntioxidants2076-39212023-01-0112222610.3390/antiox12020226Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear CellsIldete L. Ferreira0Solange Costa1Bruno J. Moraes2Ana Costa3Olga Fokt4Daniela Marinho5Vera Alves6Isabel P. Baptista7A. Cristina Rego8CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalInstitute of Periodontology, Dentistry Department, Faculty of Medicine, University of Coimbra, Avenida Bissaya Barreto, 3000-075 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalInstitute of Periodontology, Dentistry Department, Faculty of Medicine, University of Coimbra, Avenida Bissaya Barreto, 3000-075 Coimbra, PortugalInstitute of Periodontology, Dentistry Department, Faculty of Medicine, University of Coimbra, Avenida Bissaya Barreto, 3000-075 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalInstitute of Immunology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, PortugalInstitute of Periodontology, Dentistry Department, Faculty of Medicine, University of Coimbra, Avenida Bissaya Barreto, 3000-075 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalPeriodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compared to PDT, T2D patients, and control individuals. PBMCs were analyzed for mitochondrial respiration, reactive oxygen species, antioxidant proteins, and expression of Nrf2-target genes. PDT and T2D-PDT patients exhibited altered periodontal clinical markers, while T2D and T2D-PDT patients displayed increased blood HbA1c. Decreased oxygen consumption and ATP production were observed in the PDT patient’s PBMCs. PDT and T2D-PDT PBMCs also evidenced increased H<sub>2</sub>O<sub>2</sub> levels and reduced catalase levels (also detected in T2D patients), whereas a compromised glutathione cycle was observed in T2D-PDT patients. PBMCs from both T2D or T2D-PDT patients showed increased Nrf2 protein levels, enhanced GCL activity and GCL-catalytic subunit protein levels, and maintained GCLc, GST, and HO-1 mRNA levels. In contrast, the expressions of Nrf2-target genes were significantly diminished in the PDT patient’s PBMCs. Decreased SOD1 and GST mRNA levels were also observed in CD3+CD8+-lymphocytes derived from PDT and T2D-PDT patients. In conclusion, PBMCs from T2D-PDT patients showed major redox changes, while mononuclear cells from PDT patients showed mitochondrial deregulation and reduced expression of Nrf2-target genes.https://www.mdpi.com/2076-3921/12/2/226periodontitistype 2 diabetes mellitusoxidative stressmitochondriaglutathioneperipheral blood mononuclear cells |
| spellingShingle | Ildete L. Ferreira Solange Costa Bruno J. Moraes Ana Costa Olga Fokt Daniela Marinho Vera Alves Isabel P. Baptista A. Cristina Rego Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells Antioxidants periodontitis type 2 diabetes mellitus oxidative stress mitochondria glutathione peripheral blood mononuclear cells |
| title | Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells |
| title_full | Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells |
| title_fullStr | Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells |
| title_full_unstemmed | Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells |
| title_short | Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells |
| title_sort | mitochondrial and redox changes in periodontitis and type 2 diabetes human blood mononuclear cells |
| topic | periodontitis type 2 diabetes mellitus oxidative stress mitochondria glutathione peripheral blood mononuclear cells |
| url | https://www.mdpi.com/2076-3921/12/2/226 |
| work_keys_str_mv | AT ildetelferreira mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT solangecosta mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT brunojmoraes mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT anacosta mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT olgafokt mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT danielamarinho mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT veraalves mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT isabelpbaptista mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells AT acristinarego mitochondrialandredoxchangesinperiodontitisandtype2diabeteshumanbloodmononuclearcells |