ROS-Induced DNA Damage Associates with Abundance of Mitochondrial DNA in White Blood Cells of the Untreated Schizophrenic Patients

Abstract

Objective The aim of this study was (1) to examine the leukocyte mtDNA copy number (CN) in unmedicated (SZ (m−)) and medicated (SZ (m+)) male patients with paranoid schizophrenia (SZ) in comparison with the healthy male controls (HC) and (2) to compare the leukocyte mtDNA CN with the content of an oxidation marker 8-oxodG in lymphocytes of the SZ (m−) patients. Methods We evaluated leukocyte mtDNA CN of 110 subjects with SZ in comparison with 60 male HC by the method qPCR (ratio mtDNA/nDNA (gene B2M) was detected). SZ patients were divided into two subgroups. The patients of the subgroups SZ (m+) (N = 55) were treated with standard antipsychotic medications in the hospital. The patients of the subgroup SZ (m−) (N = 55) were not treated before venous blood was sampled. To evaluate oxidative DNA damage, we quantified the levels of 8-oxodG in lymphocytes (flow cytometry) of SZ (m−) patients (N = 55) and HC (N = 30). Results The leukocyte mtDNA CN showed no significant difference in SZ (m+) patients and HC. The mtDNA CN in the unmedicated subgroup SZ (m−) was significantly higher than that in the SZ (m+) subgroup or in HC group. The level of 8-oxodG in the subgroup SZ (m−) was significantly higher than that in HC group. Conclusion The leukocytes of the unmedicated SZ male patients with acute psychosis contain more mtDNA than the leukocytes of the male SZ patients treated with antipsychotic medications or the healthy controls. MtDNA content positively correlates with the level of 8-oxodG in the unmedicated SZ patients.

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“…In the present study we showed, with this specific concentration, that the copy-number of mtDNA increased significantly after 24-h treatment (data not shown), a sensitive index indicating cellular oxidative stress, inflammation and mitochondrial dysfunction [50,51]. Our result is in accordance with previous work showing an association between an altered mtDNA copy-number and cellular stress/schizophrenia pathology [52][53][54]. We found that treatment for 24 h significantly increased the copy number of mtDNA.…”

1Q12 Loci Movement in the Interphase Nucleus Under the Action of ROS Is an Important Component of the Mechanism That Determines Copy Number Variation of Satellite III (1q12) in Health and Schizophrenia

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Ribosomal DNA as DAMPs Signal for MCF7 Cancer Cells

“…TR-rDNA analysis by qPCR method and primers for mtDNA and TR-rDNA are described earlier (44, 46). 8-oxoguanine DNA glycosylase (fpg) were used for gDNA hydrolysis under manufacturer's protocol (Merck).…”