Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function
Ca2+ is an important intracellular second messenger known to regulate several cellular functions. This research aimed to investigate the mechanisms of exercise-induced immunosuppression by measuring intracellular calcium levels, Ca2+-regulating gene expression, and agonist-evoked proliferation of mu...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:12e3b42523164888b53090fd1db7870c2021-12-01T08:21:43ZExcessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function1664-042X10.3389/fphys.2021.728625https://doaj.org/article/12e3b42523164888b53090fd1db7870c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.728625/fullhttps://doaj.org/toc/1664-042XCa2+ is an important intracellular second messenger known to regulate several cellular functions. This research aimed to investigate the mechanisms of exercise-induced immunosuppression by measuring intracellular calcium levels, Ca2+-regulating gene expression, and agonist-evoked proliferation of murine splenic T lymphocytes. Mice were randomly assigned to the control, sedentary group (C), and three experimental groups, which performed a single bout of intensive and exhaustive treadmill exercise. Murine splenic lymphocytes were separated by density-gradient centrifugation immediately (E0), 3h (E3), and 24h after exercise (E24). Fura-2/AM was used to monitor cytoplasmic free Ca2+ concentration in living cells. The combined method of carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling and flow cytometry was used for the detection of T cell proliferation. The transcriptional level of Ca2+-regulating genes was quantified by using qPCR. Both basal intracellular Ca2+ levels and agonist (ConA, OKT3, or thapsigargin)-induced Ca2+ transients were significantly elevated at E3 group (p<0.05 vs. control). However, mitogen-induced cell proliferation was significantly decreased at E3 group (p<0.05 vs. control). In parallel, the transcriptional level of plasma membrane Ca2+-ATPases (PMCA), sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), TRPC1, and P2X7 was significantly downregulated, and the transcriptional level of IP3R2 and RyR2 was significantly upregulated in E3 (p<0.01 vs. control). In summary, this study demonstrated that acute exercise affected intracellular calcium homeostasis, most likely by enhancing transmembrane Ca2+ influx into cells and by reducing expression of Ca2+-ATPases such as PMCA and SERCA. However, altered Ca2+ signals were not transduced into an enhanced T cell proliferation suggesting other pathways to be responsible for the transient exercise-associated immunosuppression.Renyi LiuRenyi LiuKarsten KrügerChristian PilatWei FanYu XiaoMichael SeimetzRobert RingseisEveline Baumgart-VogtKlaus EderNorbert WeissmannFrank Christoph MoorenFrontiers Media S.A.articleacute exerciseFura-2(AM)intracellular Ca2+calcium homeostasiscell proliferationcalcium channelsPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021) |
| institution |
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DOAJ |
| language |
EN |
| topic |
acute exercise Fura-2(AM) intracellular Ca2+ calcium homeostasis cell proliferation calcium channels Physiology QP1-981 |
| spellingShingle |
acute exercise Fura-2(AM) intracellular Ca2+ calcium homeostasis cell proliferation calcium channels Physiology QP1-981 Renyi Liu Renyi Liu Karsten Krüger Christian Pilat Wei Fan Yu Xiao Michael Seimetz Robert Ringseis Eveline Baumgart-Vogt Klaus Eder Norbert Weissmann Frank Christoph Mooren Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function |
| description |
Ca2+ is an important intracellular second messenger known to regulate several cellular functions. This research aimed to investigate the mechanisms of exercise-induced immunosuppression by measuring intracellular calcium levels, Ca2+-regulating gene expression, and agonist-evoked proliferation of murine splenic T lymphocytes. Mice were randomly assigned to the control, sedentary group (C), and three experimental groups, which performed a single bout of intensive and exhaustive treadmill exercise. Murine splenic lymphocytes were separated by density-gradient centrifugation immediately (E0), 3h (E3), and 24h after exercise (E24). Fura-2/AM was used to monitor cytoplasmic free Ca2+ concentration in living cells. The combined method of carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling and flow cytometry was used for the detection of T cell proliferation. The transcriptional level of Ca2+-regulating genes was quantified by using qPCR. Both basal intracellular Ca2+ levels and agonist (ConA, OKT3, or thapsigargin)-induced Ca2+ transients were significantly elevated at E3 group (p<0.05 vs. control). However, mitogen-induced cell proliferation was significantly decreased at E3 group (p<0.05 vs. control). In parallel, the transcriptional level of plasma membrane Ca2+-ATPases (PMCA), sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), TRPC1, and P2X7 was significantly downregulated, and the transcriptional level of IP3R2 and RyR2 was significantly upregulated in E3 (p<0.01 vs. control). In summary, this study demonstrated that acute exercise affected intracellular calcium homeostasis, most likely by enhancing transmembrane Ca2+ influx into cells and by reducing expression of Ca2+-ATPases such as PMCA and SERCA. However, altered Ca2+ signals were not transduced into an enhanced T cell proliferation suggesting other pathways to be responsible for the transient exercise-associated immunosuppression. |
| format |
article |
| author |
Renyi Liu Renyi Liu Karsten Krüger Christian Pilat Wei Fan Yu Xiao Michael Seimetz Robert Ringseis Eveline Baumgart-Vogt Klaus Eder Norbert Weissmann Frank Christoph Mooren |
| author_facet |
Renyi Liu Renyi Liu Karsten Krüger Christian Pilat Wei Fan Yu Xiao Michael Seimetz Robert Ringseis Eveline Baumgart-Vogt Klaus Eder Norbert Weissmann Frank Christoph Mooren |
| author_sort |
Renyi Liu |
| title |
Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function |
| title_short |
Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function |
| title_full |
Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function |
| title_fullStr |
Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function |
| title_full_unstemmed |
Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function |
| title_sort |
excessive accumulation of intracellular ca2+ after acute exercise potentiated impairment of t-cell function |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/12e3b42523164888b53090fd1db7870c |
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