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Physical exercise induces rapid release of small extracellular vesicles into the circulation.

Frühbeis C, Helmig S, Tug S, Simon P, Krämer-Albers EM - J Extracell Vesicles (2015)

Bottom Line: Here, we show that physical activity is associated with the release of nano-sized EVs into the circulation.In response to treadmill running, elevation of small EVs was moderate but appeared more sustained.We hypothesize that EVs released during physical activity may participate in cell communication during exercise-mediated adaptation processes that involve signalling across tissues and organs.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cell Biology, Johannes Gutenberg-University Mainz, Mainz, Germany.

ABSTRACT
Cells secrete extracellular vesicles (EVs) by default and in response to diverse stimuli for the purpose of cell communication and tissue homeostasis. EVs are present in all body fluids including peripheral blood, and their appearance correlates with specific physiological and pathological conditions. Here, we show that physical activity is associated with the release of nano-sized EVs into the circulation. Healthy individuals were subjected to an incremental exercise protocol of cycling or running until exhaustion, and EVs were isolated from blood plasma samples taken before, immediately after and 90 min after exercise. Small EVs with the size of 100-130 nm, that carried proteins characteristic of exosomes, were significantly increased immediately after cycling exercise and declined again within 90 min at rest. In response to treadmill running, elevation of small EVs was moderate but appeared more sustained. To delineate EV release kinetics, plasma samples were additionally taken at the end of each increment of the cycling exercise protocol. Release of small EVs into the circulation was initiated in an early phase of exercise, before the individual anaerobic threshold, which is marked by the rise of lactate. Taken together, our study revealed that exercise triggers a rapid release of EVs with the characteristic size of exosomes into the circulation, initiated in the aerobic phase of exercise. We hypothesize that EVs released during physical activity may participate in cell communication during exercise-mediated adaptation processes that involve signalling across tissues and organs.

No MeSH data available.


Related in: MedlinePlus

Kinetic analysis of small EV release during incremental cycling exercise. Kinetics of exosome, lactate (a–d) and cfDNA (e) release were recorded during and after an incremental cycling exercise (n=2, same subject). Plasma samples taken after each increment and post exercise were subjected to differential centrifugation, and small EVs were analyzed by Western blot (a). Western Blot signals were quantified for Flot1 (b, n=2), Hsp/Hsc70 (c, n=1) and IntαIIb (d, n=1). The individual anaerobic threshold (IAT) is indicated as vertical dashed line.
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Figure 0004: Kinetic analysis of small EV release during incremental cycling exercise. Kinetics of exosome, lactate (a–d) and cfDNA (e) release were recorded during and after an incremental cycling exercise (n=2, same subject). Plasma samples taken after each increment and post exercise were subjected to differential centrifugation, and small EVs were analyzed by Western blot (a). Western Blot signals were quantified for Flot1 (b, n=2), Hsp/Hsc70 (c, n=1) and IntαIIb (d, n=1). The individual anaerobic threshold (IAT) is indicated as vertical dashed line.

Mentions: To assess the release kinetics of small EVs/exosomes during exercise, we collected blood samples after every increment of cycling exercise and purified small EVs as described above (1 subject and 2 independent experiments). The cycling protocol was chosen, since it allows convenient blood extraction at the increments and revealed robust release of small EVs in the previous experiments. By Western blotting, 100,000×g pellets were analyzed for the EV proteins Flot1, Hsc/Hsp70 and platelet-derived IntαIIb (Fig. 4a). The obtained signals were quantified and plotted against time and power. EV amounts started to increase after 9 min (150 W), rose more or less constantly to reach the maximum between 15 and 21 min (250–300 W) and started to decline 10 min post exercise (Fig. 4b–d). In addition, we determined lactate concentrations and the levels of cfDNA, which have been shown to rise during exercise with release kinetics similar to lactate (38,39). Lactate levels began to elevate after 15 min (250 W), and the IAT was reached at 289 (±8) W, demonstrating that small EV release is initiated before the IAT and the accumulation of lactate and acidification of blood (Fig. 4b–e). cfDNA concentrations started to rise after 15 min (250 W) and reached the maximum 10 min after cessation of exercise (Fig. 4e), providing evidence that secretion of small EVs and cfDNA release is 2 independent mechanistic events. Thus, small EV release is triggered early during exercise and occurs before lactate and cfDNA release.


Physical exercise induces rapid release of small extracellular vesicles into the circulation.

Frühbeis C, Helmig S, Tug S, Simon P, Krämer-Albers EM - J Extracell Vesicles (2015)

Kinetic analysis of small EV release during incremental cycling exercise. Kinetics of exosome, lactate (a–d) and cfDNA (e) release were recorded during and after an incremental cycling exercise (n=2, same subject). Plasma samples taken after each increment and post exercise were subjected to differential centrifugation, and small EVs were analyzed by Western blot (a). Western Blot signals were quantified for Flot1 (b, n=2), Hsp/Hsc70 (c, n=1) and IntαIIb (d, n=1). The individual anaerobic threshold (IAT) is indicated as vertical dashed line.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4491306&req=5

Figure 0004: Kinetic analysis of small EV release during incremental cycling exercise. Kinetics of exosome, lactate (a–d) and cfDNA (e) release were recorded during and after an incremental cycling exercise (n=2, same subject). Plasma samples taken after each increment and post exercise were subjected to differential centrifugation, and small EVs were analyzed by Western blot (a). Western Blot signals were quantified for Flot1 (b, n=2), Hsp/Hsc70 (c, n=1) and IntαIIb (d, n=1). The individual anaerobic threshold (IAT) is indicated as vertical dashed line.
Mentions: To assess the release kinetics of small EVs/exosomes during exercise, we collected blood samples after every increment of cycling exercise and purified small EVs as described above (1 subject and 2 independent experiments). The cycling protocol was chosen, since it allows convenient blood extraction at the increments and revealed robust release of small EVs in the previous experiments. By Western blotting, 100,000×g pellets were analyzed for the EV proteins Flot1, Hsc/Hsp70 and platelet-derived IntαIIb (Fig. 4a). The obtained signals were quantified and plotted against time and power. EV amounts started to increase after 9 min (150 W), rose more or less constantly to reach the maximum between 15 and 21 min (250–300 W) and started to decline 10 min post exercise (Fig. 4b–d). In addition, we determined lactate concentrations and the levels of cfDNA, which have been shown to rise during exercise with release kinetics similar to lactate (38,39). Lactate levels began to elevate after 15 min (250 W), and the IAT was reached at 289 (±8) W, demonstrating that small EV release is initiated before the IAT and the accumulation of lactate and acidification of blood (Fig. 4b–e). cfDNA concentrations started to rise after 15 min (250 W) and reached the maximum 10 min after cessation of exercise (Fig. 4e), providing evidence that secretion of small EVs and cfDNA release is 2 independent mechanistic events. Thus, small EV release is triggered early during exercise and occurs before lactate and cfDNA release.

Bottom Line: Here, we show that physical activity is associated with the release of nano-sized EVs into the circulation.In response to treadmill running, elevation of small EVs was moderate but appeared more sustained.We hypothesize that EVs released during physical activity may participate in cell communication during exercise-mediated adaptation processes that involve signalling across tissues and organs.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cell Biology, Johannes Gutenberg-University Mainz, Mainz, Germany.

ABSTRACT
Cells secrete extracellular vesicles (EVs) by default and in response to diverse stimuli for the purpose of cell communication and tissue homeostasis. EVs are present in all body fluids including peripheral blood, and their appearance correlates with specific physiological and pathological conditions. Here, we show that physical activity is associated with the release of nano-sized EVs into the circulation. Healthy individuals were subjected to an incremental exercise protocol of cycling or running until exhaustion, and EVs were isolated from blood plasma samples taken before, immediately after and 90 min after exercise. Small EVs with the size of 100-130 nm, that carried proteins characteristic of exosomes, were significantly increased immediately after cycling exercise and declined again within 90 min at rest. In response to treadmill running, elevation of small EVs was moderate but appeared more sustained. To delineate EV release kinetics, plasma samples were additionally taken at the end of each increment of the cycling exercise protocol. Release of small EVs into the circulation was initiated in an early phase of exercise, before the individual anaerobic threshold, which is marked by the rise of lactate. Taken together, our study revealed that exercise triggers a rapid release of EVs with the characteristic size of exosomes into the circulation, initiated in the aerobic phase of exercise. We hypothesize that EVs released during physical activity may participate in cell communication during exercise-mediated adaptation processes that involve signalling across tissues and organs.

No MeSH data available.


Related in: MedlinePlus