scholarly journals Mitochondrial Function in Peripheral Blood Mononuclear Cells (PBMC) Is Enhanced, Together with Increased Reactive Oxygen Species, in Severe Asthmatic Patients in Exacerbation

2019 ◽  
Vol 8 (10) ◽  
pp. 1613 ◽  
Author(s):  
Ederlé ◽  
Charles ◽  
Khayath ◽  
Poirot ◽  
Meyer ◽  
...  

asthma is a chronic inflammatory lung syndrome with an increasing prevalence and a rare but significant risk of death. Its pathophysiology is complex, and therefore we investigated at the systemic level a potential implication of oxidative stress and of peripheral blood mononuclear cells’ (PBMC) mitochondrial function. Twenty severe asthmatic patients with severe exacerbation (GINA 4–5) and 20 healthy volunteers participated at the study. Mitochondrial respiratory chain complexes activities using different substrates and reactive oxygen species (ROS) production were determined in both groups by high-resolution respirometry and electronic paramagnetic resonance, respectively. Healthy PBMC were also incubated with a pool of plasma of severe asthmatics or healthy controls. Mitochondrial respiratory chain complexes activity (+52.45%, p = 0.015 for VADP) and ROS production (+34.3%, p = 0.02) were increased in asthmatic patients. Increased ROS did not originate mainly from mitochondria. Plasma of severe asthmatics significantly increased healthy PBMC mitochondrial dioxygen consumption (+56.8%, p = 0.031). In conclusion, such asthma endotype, characterized by increased PMBCs mitochondrial oxidative capacity and ROS production likely related to a plasma constituent, may reflect activation of the immune system. Further studies are needed to determine whether increased PBMC mitochondrial respiration might have protective effects, opening thus new therapeutic approaches.

2019 ◽  
Vol 2 (31) ◽  
pp. 16-19
Author(s):  
L. G. Mishura ◽  
L. B. Gaikovaya ◽  
G. G. Rodionov ◽  
V. A. Dadali

Mitochondrial respiratory chain enzyme activities were determined by spectrophotometric enzyme assay in lymphocytes of 100 patients with acute myocardial infarction. A significant decrease in the activity of complexes II–III and IV and an increase in the activity of complex I of the respiratory chain were found. According to the correlation analysis, the feedback of troponin T and I concentrations in the serum and the activity of complex IV of the respiratory chain was detected. A decrease in the activity of the IV complex of the mitochondrial lymphocyte respiratory chain below 2.87 IU/g of protein indicates an increased level of clinical risk in patients with acute myocardial infarction.


2019 ◽  
Author(s):  
Yun Sun ◽  
Bin Gu ◽  
Yan Qian ◽  
Yi Chen ◽  
Zheng-dao Mao ◽  
...  

Abstract Backgroud To explore the Effect of grape seed proanthocyanidin extract(GSPE) in peripheral blood mononuclear cells of severe asthmatic patients. Methods 40 severe asthmatic patients were randomly and averagely divided into 2 groups: DXM group (n=20) and GSPE+DXM group (n=20), and 20 healthy volunteers as control gorup. Heparinized peripheral venous blood from each subject was collected in a sterile vacuum tube. The levels of interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 were detected by ELISA. The protein and mRNA expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2), glutamatecysteine ligase modifier subunit (GCLM) inducible nitric oxide synthase (iNOS) and inactivation of histone deacetylase-2 (HDAC2) were detected by Western blot and qRT-PCR respectively. Glutathion(GSH) was measured by using Glutathione Fluorometric Detection Kit, and Nrf2-ARE binding ability was measured by using TransAM Nrf2 Transcription Factor ELISA Kit. Results The results showed that the levels of IL-8 and MCP-1 in normal control group were lower than those in severe asthma group (P <0.05). Treatment with GSPE+DXM reduced the levels of IL-8 and MCP-1 significantly when compared with DXM only ( P <0.05).The mRNA expression of iNOS in DXM group was significantly higher than that in control group. However, after adding GSPE treatment, the expression dramatically decreased ( P <0.001). On the contrary, lower mRNA expressions of Nrf2, GCLM and HDAC2 were found in DXM group than in control group ( P <0.001). Accordingly, when treated with GSPE, these expressions elevated and reached a statistical significance ( P <0.05). Consistently, the results from western blot analysis confirmed the role of GSPE on the protein expressions of iNOS, Nrf2, GCLM and HDAC2 in PBMCs of patients with severe asthma ( P <0.001). The PBMCs from patients with severe asthma exhibited lower Nrf2-ARE binding ability and produced less GSH than normal controls. GSPE treatment effectively augmented the Nrf2-ARE binding ability and the expression of GSH, which demonstrated the biological antioxidant potential of GSPE ( P <0.001). Conclusion GSPE can alleviate glucocorticoid resistance by regulating Nrf2-iNOS-HDAC2 signaling pathway in severe asthma, suggesting that GSPE have potential clinical application prospects in the treatment of severe asthma.


2020 ◽  
Author(s):  
Yun Sun ◽  
Bin Gu ◽  
Yan Qian ◽  
Yi Chen ◽  
Zheng-dao Mao ◽  
...  

Abstract Backgroud To explore the Effect of grape seed proanthocyanidin extract(GSPE) in peripheral blood mononuclear cells of severe asthmatic patients. Methods 40 severe asthmatic patients were randomly and averagely divided into 2 groups: DXM group (n=20) and GSPE+DXM group (n=20), and 20 healthy volunteers as control gorup. Heparinized peripheral venous blood from each subject was collected in a sterile vacuum tube. The levels of interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 were detected by ELISA. The protein and mRNA expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2), glutamatecysteine ligase modifier subunit (GCLM) inducible nitric oxide synthase (iNOS) and inactivation of histone deacetylase-2 (HDAC2) were detected by Western blot and qRT-PCR respectively. Glutathion(GSH) was measured by using Glutathione Fluorometric Detection Kit, and Nrf2-ARE binding ability was measured by using TransAM Nrf2 Transcription Factor ELISA Kit. Results The results showed that the levels of IL-8 and MCP-1 in normal control group were lower than those in severe asthma group (P <0.05). Treatment with GSPE+DXM reduced the levels of IL-8 and MCP-1 significantly when compared with DXM only ( P <0.05).The mRNA expression of iNOS in DXM group was significantly higher than that in control group. However, after adding GSPE treatment, the expression dramatically decreased ( P <0.001). On the contrary, lower mRNA expressions of Nrf2, GCLM and HDAC2 were found in DXM group than in control group ( P <0.001). Accordingly, when treated with GSPE, these expressions elevated and reached a statistical significance ( P <0.05). Consistently, the results from western blot analysis confirmed the role of GSPE on the protein expressions of iNOS, Nrf2, GCLM and HDAC2 in PBMCs of patients with severe asthma ( P <0.001). The PBMCs from patients with severe asthma exhibited lower Nrf2-ARE binding ability and produced less GSH than normal controls. GSPE treatment effectively augmented the Nrf2-ARE binding ability and the expression of GSH, which demonstrated the biological antioxidant potential of GSPE ( P <0.001). Conclusion GSPE can alleviate glucocorticoid resistance by regulating Nrf2-iNOS-HDAC2 signaling pathway in severe asthma, suggesting that GSPE have potential clinical application prospects in the treatment of severe asthma.


2009 ◽  
Vol 2 (5) ◽  
pp. 317-321 ◽  
Author(s):  
Camila Armond Isoni ◽  
Érica Abreu Borges ◽  
Clara Araújo Veloso ◽  
Rafael Teixeira Mattos ◽  
Miriam Martins Chaves ◽  
...  

Peripheral blood mononuclear cells (PBMNC) from patients with type 2 diabetes (DM2) have generated higher levels of reactive oxygen species (ROS) that were higher than those in cells from healthy individuals. In the presence of a cAMP-elevating agent, ROS production was significantly activated in PBMNC from DM2 patients but it was inhibited in cells from healthy subjects. Higher levels of IL-6 has been detected in the supernatant of PBMNC cultures from DM2 patients in comparison with healthy controls. When cells were cultured in the presence of a cAMP-elevating agent, the level of IL-6 decreased has by 46% in the supernatant of PBMNC from DM2 patients but it remained unaltered in controls. No correlations between ROS and IL-6 levels in PBMNC from DM2 patients or controls have been observed. Secretions of IL-4 or IFN by PBMNC from patients or controls have not been affected by the elevation of cAMP. cAMP elevating agents have activated the production of harmful reactive oxidant down modulated IL-6 secretion by these cells from DM2 patients, suggesting an alteration in the metabolic response possibly due to hyperglicemia. The results suggest that cAMP may play an important role in the pathogenesis of diabetes.


2018 ◽  
Vol 40 (5) ◽  
pp. 387-392 ◽  
Author(s):  
Ana Paula Fortes dos Santos Thomazelli ◽  
Fernanda Tomiotto-Pellissier ◽  
Milena Menegazzo Miranda-Sapla ◽  
Suelen Santos da Silva ◽  
Daniele Sapede Alvarenga ◽  
...  

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