Release of bulk cell free DNA during physical exercise occurs independent of extracellular vesicles

Helmig, Susanne; Frühbeis, Carsten; Krämer-Albers, Eva-Maria; Simon, Perikles; Tug, Suzan

doi:10.1007/s00421-015-3207-8

Cited by 63 publications

(68 citation statements)

References 56 publications

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“…These two afore mentioned reports on exercise–induced decline in cf mt-DNA are also consistent to our finding of gradual decrease in pre-exercise cf mt-DNA over the study period involving three bouts of exhaustive treadmill exercise. It should be pointed out that only in our study, in contrast to other investigations [15,16,32], a significant increase in post-exercise cf mt-DNA was found. This discrepancy may result from: (a) differences in the study protocols–we analyzed the effect of three repeated bouts of exhaustive treadmill exercise separated by 72 hours of resting while other researches described the effect of single bout of exercise on cf mt-DNA concentration; (b) more intense exercise performed by our volunteers that in terms of induction of cf n-DNA response could be equivalent to half-marathon [11] and may also stimulate increased release of cf mt-DNA.…”

Section: Discussioncontrasting

confidence: 99%

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Repeated bouts of exhaustive exercise increase circulating cell free nuclear and mitochondrial DNA without development of tolerance in healthy men

et al. 2017

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ObjectiveAcute single strenuous exercise increases circulating cell free DNA (cf DNA). We tested whether three repeated bouts of exhaustive exercise induced the cf DNA response without development of tolerance in healthy men.MethodsEleven average-trained men (age 34.0±5.2 years, body mass index 26.2±3.1 kg/m2, maximal oxygen consumption—VO2max 49.6±4.5 ml/kg*min) performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 hours of resting. Blood was collected before and after each bout of exercise for determination of cell free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, selected markers of muscle damage, and blood cell count.ResultsEach bout induced the increase (p<0.05) in plasma cf n-DNA: from 3.4±1.4 to 38.5±27.5, from 4.1±3.3 to 48.5±26.2, and 3.1±1.6 to 53.8±39.9 ng/mL after the first, second, and third exercise, respectively. In a congruent way, cf mt-DNA rose significantly after the second (from 229±216 to 450±228*103 GE/mL) and third bout of exercise (from 173±120 to 462±314*103 GE/mL).Pre-exercise cf mt-DNA decreased (p<0.05) by 2-times (from 355±219 before the first bout to 173±120*103 GE/mL before the third bout) over the study period and were accompanied by significant increase in white blood cells, platelets, creatine kinase, creatinine and lactate after each bout. However, the exercise induced percentage increment of cf n-DNA was always many times higher than corresponding increments of the afore-mentioned markers at any occasion.ConclusionsRepeated bouts of exhaustive exercise induced remarkable increase in circulating cf n-DNA without signs of tolerance development. Baseline cf mt-DNA decreased in response to series of strenuous exercise. Since percentage increments of cf n-DNA in response to exercise were many times higher than those observed for other markers, measurement of circulating cf n-DNA could be a sensitive tool for monitoring acute exercise effects in human body.

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Section: Discussioncontrasting

confidence: 99%

“…This is in line with previous studies reporting lack of significant increase in circulating cf mt-DNA just after single exhaustive exercise [16, 32]. On the other hand, prolonged moderate exercise (90 min treadmill run at 60% of VO2 max) caused the decrease in cf mt-DNA in healthy moderately trained young men [15].…”

Section: Discussionsupporting

confidence: 92%

Repeated bouts of exhaustive exercise increase circulating cell free nuclear and mitochondrial DNA without development of tolerance in healthy men

et al. 2017

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“…While generally, cf‐nDNA has been localized to soluble plasma fractions, cf‐mDNA was shown to be largely associated with particulate microvesicles in plasma pelleted 30 min at 10,000 g (Helmig et al. ). Our plasma samples for cf‐mDNA isolation were centrifuged 5 min at 800 g and 5–7 min at 2600 g (to remove platelets harboring mitochondria), so it is likely that microvesicle‐associated cf‐mDNA was retained in the samples.…”

Section: Discussionmentioning

confidence: 99%

Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise

et al. 2016

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Increased plasma cell‐free mitochondrial DNA (cf‐mDNA), a damage‐associated molecular pattern (DAMP) produced by cellular injury, contributes to neutrophil activation/inflammation in trauma patients and arises in cancer and autoimmunity. To further understand relationships between cf‐mDNA released by tissue injury, inflammation, and health benefits of exercise, we examined cf‐mDNA response to prolonged moderate aerobic exercise. Seven healthy moderately trained young men (age = 22.4 ± 1.2) completed a treadmill exercise trial for 90 min at 60% VO 2 max and a resting control trial. Blood was sampled immediately prior to exercise (0 min = baseline), during (+18, +54 min), immediately after (+90 min), and after recovery (R40). Plasma was analyzed for cf‐mDNA, IL‐6, and lactate. A significant difference in cf‐mDNA response was observed between exercise and control trials, with cf‐mDNA levels reduced during exercise at +54 and +90 (with or without plasma volume shift correction). Declines in cf‐mDNA were accompanied by increased lactate and followed by an increase in IL‐6, suggesting a temporal association with muscle stress and inflammatory processes. Our novel finding of cf‐mDNA decline with prolonged moderate treadmill exercise provides evidence for increased clearance from or reduced release of cf‐mDNA into the blood with prolonged exercise. These studies contrast with previous investigations involving exhaustive short‐term treadmill exercise, in which no change in cf‐mDNA levels were reported, and contribute to our understanding of differences between exercise‐ and trauma‐induced inflammation. We propose that transient declines in cf‐mDNA may induce health benefits, by reducing systemic inflammation.

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“…The alarmins HMGB-1 and cfDNA return to baseline levels within 30 and 90 minutes respectively post-exercise [18,65]. With exercise of high impact and greater duration, such as half and ultra-marathons, the cfDNA takes around two hours to return to baseline [34,66].…”

Section: Recognition Of Exercise Induced Muscle Damage and Innate Immmentioning

confidence: 99%

“…Alarmins collectively include a range of host cell derived products including nuclear or mitochondrial DNA [18,19], ATP, intra-and extracellular proteins such as chaperone [20][21][22][23] or cytoskeletal proteins like tenascin C (TSC) [24] nuclear proteins including high mobility group box protein-1 (HMGB-1) [25][26][27] and cytokines such as IL-1a and IL-33 (Table 1) [28,29]. The binding of PAMPs or DAMPs/ alarmins to specific PRRs can elicit a cytokine response by host cells that promotes the recruitment of innate leukocytes to the site of tissue damage.…”

Section: Introductionmentioning

confidence: 99%

The Role of the Innate and Adaptive Immunity in Exercise Induced Muscle Damage and Repair

Jones¹,

Hoyne²

2017

J Clin Cell Immunol

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The immune system plays a crucial role in regulating tissue repair processes following damage. The cellular basis of tissue repair has best been studied in toxin-induced models due to their reliability and reproducible kinetics. These models have established a crucial role for innate and adaptive immune cells that follow a temporally regulated response that begins with a proinflammatory response that is subsequently replaced by a regulatory type 2 immune response to facilitate tissue repair and restore homeostasis. Inflammation is a crucial first response to cell damage that is modulated by the response of innate lymphoid cells and tissue resident regulatory T cells. In this review we examine the process of exercise induced muscle damage to provide comparisons of how this may follow a similar coordinated response as that mediated by toxin induced damage.

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Release of bulk cell free DNA during physical exercise occurs independent of extracellular vesicles

Cited by 63 publications

References 56 publications

Repeated bouts of exhaustive exercise increase circulating cell free nuclear and mitochondrial DNA without development of tolerance in healthy men

Repeated bouts of exhaustive exercise increase circulating cell free nuclear and mitochondrial DNA without development of tolerance in healthy men

Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise

The Role of the Innate and Adaptive Immunity in Exercise Induced Muscle Damage and Repair

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