Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR-based assay

Movassaghi, Shafieh; Jafari, Sara; Falahati, Kowsar; Ataei, Mitra; Sanati, Mohammad Hossein; Jadali, Zohreh

doi:10.1016/j.abd.2019.11.003

Cited by 9 publications

(4 citation statements)

References 29 publications

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“…It is known that most studies on mtDNA copy number in diseases associated with mitochondrial dysfunction demonstrate a decrease in mtDNA copy number compared to healthy controls (Ding et al, 2023;Malik, 2023). The previous study on the number of mtDNA copies in the peripheral blood of patients with SSc showed that mtDNA copy number was lower in SSc patients in comparison with healthy participants of the study (Movassaghi et al, 2020). It can be assumed that the differences in mtDNA copy number between SSc and control groups in the current study did not reach statistical significance due to insufficient sample size, while the published study included 46 patients with SSc vs. 49 healthy individuals.…”

Section: Discussionmentioning

confidence: 83%

Mitochondrial DNA copy number in patients with systemic sclerosis

Bogatyreva,

Gerasimova,

Kirichenko

et al. 2023

Front. Mol. Biosci.

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Introduction: Systemic scleroderma (SSc) is a chronic autoimmune disease of inflammatory origin. Mitochondrial dysfunction is considered as an important mechanism in the pathogenesis of SSc. Currently mitochondrial DNA (mtDNA) copy number is used as a surrogate marker of mitochondrial dysfunction. Previous studies demonstrate that innate immune cells are important participants in inflammatory and fibrotic processes in SSc. The aim of the study was to evaluate the number of mtDNA copies in CD14+ monocytes and whole blood of patients with SSc in comparison with healthy individuals.Methods: Absolute mtDNA copy number was measured using digital PCR. It was found that the number of mtDNA copies in CD14+ monocytes was significantly higher in patients with SSc compared to control, while the number of mtDNA copies in the whole blood did not have significant differences.Results: The correlation analysis revealed an inverse association of mtDNA copy number with disease duration and the relationship between pro-inflammatory activation of CD14+ monocytes in terms of LPS-stimulated IL-6 secretion and mtDNA copy number. At the same time, basal and LPS-stimulated secretion of IL-6 by cultured CD+ monocytes were significantly higher in SSc group in comparison with control.Discussion: The study results suggest that increase of mtDNA copy number in CD14+ monocytes is a possible mechanism to maintain the reduced function of defective mitochondria in monocytes from patients with SSc associated with the development and progression of SSc.

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Section: Discussionmentioning

confidence: 83%

Mitochondrial DNA copy number in patients with systemic sclerosis

Bogatyreva,

Gerasimova,

Kirichenko

et al. 2023

Front. Mol. Biosci.

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“… 39 , 45 In addition, although mtDNAcn quantification has been used as a biomarker for mitochondrial function and has been implicated in age-related diseases, 46 it is not a direct measure of the functionality of individual mitochondria and may reflect oxidative stress states rather than cellular aging itself. 44 , 47 Indeed, mtDNAcn as measured by qPCR, which reflects the relative quantity of mitochondrial DNA compared to the nuclear DNA in a sample, should be considered a proxy for the content of mitochondrial copies. Mixed findings have been also reported with respect to the direction of altered mtDNAcn in several neuropsychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

Alterations of cellular aging markers in obsessive–compulsive disorder: mitochondrial DNA copy number and telomere length

Kang

Park

Lin

et al. 2021

jpn

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Background: The present study examined whether mitochondrial DNA copy number (mtDNAcn) and telomere length — key markers of cellular aging — were altered in male and female participants with obsessive–compulsive disorder (OCD) compared to healthy controls. We also tested for associations between these alterations and OCD-related clinical features and inflammatory index. Methods: A total of 235 patients with OCD (38.7% female) and 234 healthy controls (41.5% female) were included. We quantified whole-blood mtDNAcn and leukocyte telomere length using quantitative polymerase chain reaction. We also calculated the neutrophil-to-lymphocyte ratio from complete blood cell counts. Results: Multivariate analysis of covariance showed that OCD status had a significant overall effect on cellular aging markers in men (Wilks λ = 0.889, F2,275 = 17.13, p < 0.001) and women (Wilks λ = 0.742, F2,182 = 31.61, p < 0.001) after controlling for age, body mass index and childhood trauma. In post-hoc comparisons, men with OCD had lower mtDNAcn than controls (p < 0.001), but we found no between-group difference for telomere length (p = 0.55). Women with OCD had a significantly lower mtDNAcn (p < 0.001) and shortened telomere length (p = 0.023) compared to controls. Moreover, the lower mtDNAcn shown in the OCD group was significantly correlated with an increase in systemic inflammation for both sexes, as measured by neutrophil-to-lymphocyte ratio. Limitations: The present cross‐sectional design did not allow us to infer a causal relationship between OCD disease status and cellular aging markers. Conclusion: The present study is, to our knowledge, the first to demonstrate alterations in mtDNAcn and telomere shortening in OCD. These results suggest that aging-associated molecular mechanisms may be important in the pathophysiology of OCD.

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“…Determination of mtDNA oxidative damage. 8-Hydroxyl 2'-deoxyguanosine (8-OHdG) is one of the most common markers of oxidative DNA lesions and is widely applied for the measurement of oxidative DNA damage (32,33). In the detection of oxidative damage with 8-OHdG, the marker does not deform the DNA structure but causes inhibition of Taq DNA polymerase during PCR.…”

Section: Mitochondrial Genome Sequencingmentioning

confidence: 99%

Comprehensive analysis of mitochondrial DNA variants, mitochondrial DNA copy number and oxidative damage in psoriatic arthritis

Alwehaidah,

Alsabbagh,

Al‑kafaji

2023

Biomed Rep

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Growing evidence suggests that abnormalities in mitochondrial DNA (mtDNA) are involved in the pathogenesis of various inflammatory and immuno-mediated diseases. The present study analysed the entire mitochondrial genome by next-generation sequencing (NGS) in 23 patients with psoriatic arthritis (PsA) and 20 healthy controls to identify PsA-related variants. Changes in mtDNA copy number (mtDNAcn) were also evaluated by quantitative polymerase chain reaction (qPCR) and mtDNA oxidative damage was measured using an 8-hydroxy-2'-deoxyguanosine assay. NGS analysis revealed a total of 435 variants including 187 in patients with PsA only and 122 in controls only. Additionally, 126 common variants were found, of which 2 variants differed significantly in their frequencies among patients and controls (P<0.05), and may be associated with susceptibility to PsA. A total of 33 missense variants in mtDNA-encoded genes for complexes I, III, IV and V were identified only in patients with PsA. Of them, 25 variants were predicted to be deleterious by affecting the functions and structures of encoded proteins, and 13 variants were predicted to affect protein's stability. mtDNAcn analysis revealed decreased mtDNA content in patients with PsA compared with controls (P=0.0001) but the decrease in mtDNAcn was not correlated with patients' age or inflammatory biomarkers (P>0.05). Moreover, a higher level of oxidative damage was observed in patients with PsA compared with controls (P=0.03). The results of the present comprehensive analysis of mtDNA in PsA revealed that certain mtDNA variants may be implicated in the predisposition/pathogenesis of PsA, highlighting the importance of NGS in the identification of mtDNA variants in PsA. The current results also demonstrated that decreased mtDNAcn in PsA may be a consequence of increased oxidative stress. These data provide valuable insights into the contribution of mtDNA defects to the pathogenesis of PsA. Additional studies in larger cohorts are needed to elucidate the role of mtDNA defects in PsA.

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Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR-based assay

Cited by 9 publications

References 29 publications

Mitochondrial DNA copy number in patients with systemic sclerosis

Mitochondrial DNA copy number in patients with systemic sclerosis

Alterations of cellular aging markers in obsessive–compulsive disorder: mitochondrial DNA copy number and telomere length

Comprehensive analysis of mitochondrial DNA variants, mitochondrial DNA copy number and oxidative damage in psoriatic arthritis

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