Extracellular mutant mitochondrial DNA content is dramatically elevated in the blood plasma of irradiated mice

Abdullaev, S. A.; Антипова, В. Н.; Gaziev, A.I.

doi:10.1134/s0026893309060119

Cited by 13 publications

(10 citation statements)

References 38 publications

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“…It has previously been shown that circulating cf-mtDNA from the plasma of irradiated mice contains a certain amount of mutant copies that can be detected by Surveyor nuclease (mismatch-specific plant DNA endonuclease) (Abdullaev et al 2009;Bannwarth et al 2006Bannwarth et al , 2013. The results of analyses of cf-mtDNA mutant copies in the urine of irradiated rats are consistent with previous data on the analysis of cf-mtDNA in the plasma of irradiated mice.…”

Section: Discussionsupporting

confidence: 89%

“…As mentioned above, we observed earlier an increase in the fraction of mutant cf-mtDNA copies revealed by the Surveyor nuclease assay in the plasma of X-ray-irradiated mice (Abdullaev et al 2009). The analyses of cf-mtDNA within total DNA from the urine of X-ray-irradiated rats show that transrenal cf-DNA contains a certain percentage of mutant copies of cf-mtDNA fragments (Figs.…”

Section: Resultsmentioning

confidence: 70%

“…To determine the levels of heteroplasmy of cf-mtDNA isolated from rat urine, we used Surveyor Ò Mutation Detection Kit (Transgenomic, Omaha, NE, USA), as described (Bannwarth et al 2006(Bannwarth et al , 2013Abdullaev et al 2009). Surveyor Nuclease assay for mtDNA mismatches is a much faster, more sensitive, and easier procedure to be performed than other ones ''traditionally'' mutation detection (Bannwarth et al 2006(Bannwarth et al , 2013.…”

Section: Surveyor Nuclease Assay Of Mtdna Mutationsmentioning

confidence: 99%

“…In previous studies, it was shown that the content of circulating cfmtDNA was significantly higher than that of cf-nDNA in the blood plasma of mice exposed to ionizing radiation, as well as in the plasma of patients with lung cancer during radiotherapy. The fraction of cf-mtDNA detected in the plasma of irradiated mice and in the plasma of patients contained mutations (Abdullaev et al 2009;Strelkova et al 2010). The increased release of circulating cf-DNA from tissues into the bloodstream in exposed animals reflects the enhanced cell death induced by radiation.…”

Section: Introductionmentioning

confidence: 96%

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Cell-free DNA in the urine of rats exposed to ionizing radiation

Abdullaev

Minkabirova

Bezlepkin

et al. 2015

Radiat Environ Biophys

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Investigation of cell-free DNA (cf-DNA) in body fluids, as a potential biomarker for assessing the effect of ionizing radiation on the organism, is of considerable interest. We investigated changes in the contents of cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) in the urine of X-ray-exposed rats. Assays of cf-mtDNA and cf-nDNA were performed by a real-time PCR in rat urine collected before and after irradiation of animals with doses of 3 and 5 Gy. We also determined the presence of mutations in urine cf-mtDNA, as recognized by Surveyor nuclease. A sharp increase in cf-mtDNA and cf-nDNA in the urine of irradiated rats was observed within 24 h after exposure, followed by a decrease to normal levels. In all cases, the contents of cf-mtDNA fragment copies (estimated by gene tRNA) were significantly higher than those of cf-nDNA estimated by gene GAPDH. A certain portion of mutant cf-mtDNA fragments was detected in the urine of exposed rats, whereas they were absent in the urine of the same animals before irradiation. These preliminary data also suggest that the increased levels of urine cf-mtDNA and cf-nDNA may be a potential biomarker for noninvasive assessment of how the organism responds to ionizing radiation influence.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 70%

Section: Surveyor Nuclease Assay Of Mtdna Mutationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Cell-free DNA in the urine of rats exposed to ionizing radiation

Abdullaev

Minkabirova

Bezlepkin

et al. 2015

Radiat Environ Biophys

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“…Various biological effects are induced after exposure to IR [31]. Modern radiobiology documents the phenomenon of bystander effect, whereby cells that are not traversed by IR exhibit responses like irradiated cells.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of MicroRNA expression in irradiated and bystander cells

Chaudhry

Omaruddin

2012

Mol Biol

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The ionizing radiation (IR) induces a variety of biological effects in irradiated cells. Additionally, the irradiated cells communicate with unirradiated cells and induce changes in them through a phenomenon termed as the bystander effect. The nature of the bystander effect signal and how it impacts unirradiated cells remains to be discovered. Examination of molecular changes in bystander cells due to signals from irradiated cells could lead to the identification of the pathways underlying the bystander effect. To gain insight into the molecular pathways affected by the transmission of signal from irradiated cells to bystander cells, we moni tored the microRNA (miRNA) transcriptional changes. miRNAs control gene expression at the posttran scriptional level. In previous studies from our laboratory the modulation of miRNA in irradiated human cells were identified. In the present work human lymphoblasts TK6 cells in a medium exchanged bystander effect model system were used to analyze miRNA expression alterations by employing the real time RT PCR tech nology. The relative expression of several miRNAs involved in RAS, c MYC and BCL2 gene regulation were examined. The let 7 family of miRNAs was upregulated in irradiated cells but most of these miRNAs remained repressed in bystander cells. The miR 17 3p, miR 19b, and miR-18a were upregulated in irradi ated cells but were repressed in the bystander cells. The miR 17 5p, miR 142 3p, rniR 142 5p, and miR 19a were induced only for a short time in bystander cells. The miR 15a, miR 16, miR 143, miR 145, miR 155, and miR21 were upregulated in irradiated TK6 cells. While the expression of miR 15a, miR 16, miR 155, and miR 21 was repressed, the miR 143 and miR 145 expression was induced in bystander cells. These results indicate the involvement of miRNA modulation in irradiated and bystander cells.

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Mitochondrial function and mitochondrial DNA maintenance with advancing age

2014

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We review the impact of mitochondrial DNA (mtDNA) maintenance and mitochondrial function on the aging process. Mitochondrial function and mtDNA integrity are closely related. In order to create a protective barrier against reactive oxygen and nitrogen species (RONS) attacks and ensure mtDNA integrity, multiple cellular mtDNA copies are packaged together with various proteins in nucleoids. Regulation of antioxidant and RONS balance, DNA base excision repair, and selective degradation of damaged mtDNA copies preserves normal mtDNA quantities. Oxidative damage to mtDNA molecules does not substantially contribute to increased mtDNA mutation frequency; rather, mtDNA replication errors of DNA PolG are the main source of mtDNA mutations. Mitochondrial turnover is the major contributor to maintenance of mtDNA and functionally active mitochondria. Mitochondrial turnover involves mitochondrial biogenesis, mitochondrial dynamics, and selective autophagic removal of dysfunctional mitochondria (i.e., mitophagy). All of these processes exhibit decreased activity during aging and fall under greater nuclear genome control, possibly coincident with the emergence of nuclear genome instability. We suggest that the age-dependent accumulation of mutated mtDNA copies and dysfunctional mitochondria is associated primarily with decreased cellular autophagic and mitophagic activity.

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Extracellular mutant mitochondrial DNA content is dramatically elevated in the blood plasma of irradiated mice

Cited by 13 publications

References 38 publications

Cell-free DNA in the urine of rats exposed to ionizing radiation

Cell-free DNA in the urine of rats exposed to ionizing radiation

Differential regulation of MicroRNA expression in irradiated and bystander cells

Mitochondrial function and mitochondrial DNA maintenance with advancing age

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