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Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early- and late-pubertal males.

ABSTRACT: Peripheral blood mononuclear cells (PBMCs) are stimulated by exercise and contribute not only to host defense, but also to growth, repair, and disease pathogenesis. Whether PBMC gene expression is altered by exercise in children is not known. Ten early pubertal boys (8-12 y) and 10 late pubertal boys (15-18 y) performed ten 2-min bouts of strenuous, constant work rate exercise with 1-min rest intervals. PBMCs were isolated before and after exercise and microarray (Affymetrix U133 + 2 chips) analyzed. Statistical criterion to identify gene expression changes was less than 5% false discovery rate (FDR) with 95% confidence interval. One thousand two hundred forty-six genes were altered in older boys (517 up, 729 down), but only 109 were altered in the younger group (79 up, 30 down). In older boys, 13 gene pathways (using Expression Analysis Systematic Explorer, p < 0.05) were found (e.g. natural killer cell cytotoxicity, apoptosis). Epiregulin gene expression (EREG, a growth factor involved in wound healing) increased in older boys. In older boys exercise altered genes such as TBX21, GZMA, PGTDR, and CCL5 also play roles in pediatric inflammatory diseases like asthma. Sixty-six genes were changed significantly in both groups. The pattern of PBMC gene expression suggests the initiation of an immunologic "danger" signal associated with a sudden change in energy expenditure.

SUBMITTER: Radom-Aizik S

PROVIDER: S-EPMC4065861 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early- and late-pubertal males.

Radom-Aizik Shlomit S Zaldivar Frank F Leu Szu-Yun SY Cooper Dan M DM

Pediatric research 20090401 4

Peripheral blood mononuclear cells (PBMCs) are stimulated by exercise and contribute not only to host defense, but also to growth, repair, and disease pathogenesis. Whether PBMC gene expression is altered by exercise in children is not known. Ten early pubertal boys (8-12 y) and 10 late pubertal boys (15-18 y) performed ten 2-min bouts of strenuous, constant work rate exercise with 1-min rest intervals. PBMCs were isolated before and after exercise and microarray (Affymetrix U133 + 2 chips) anal ...[more]

PMID: 19127215

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Project description:Normal tissue toxicity is a dose-limiting factor in radiation therapy. Therefore, a detailed understanding of the normal tissue response to radiation is necessary to predict the risk of normal tissue toxicity and to development strategies for tissue protection. One component of normal tissue that is continuously exposed during therapeutic irradiation is the circulating population of peripheral blood mononuclear cells (PBMC). PBMCs are highly sensitive to ionizing radiation (IR); however, little is known about how IR affects the PBMC response on a systemic level. It was the aim of this study to investigate whether IR was capable to induce changes in the composition and function of extracellular vesicles (EVs) secreted from PBMCs after radiation exposure to different doses. Therefore, whole blood samples from healthy donors were exposed to X-ray radiation in the clinically relevant doses of 0, 0.1, 2 or 6 Gy and PBMC-secreted EVs were isolated 72 h later. Proteome and miRNome analysis of EVs as well as functional studies were performed. Secreted EVs showed a dose-dependent increase in the number of significantly deregulated proteins and microRNAs. For both, proteome and microRNA data, principal component analysis showed a dose-dependent separation of control and exposed groups. Integrated pathway analysis of the radiation-regulated EV proteins and microRNAs consistently predicted an association of deregulated molecules with apoptosis, cell death and survival. Functional studies identified endothelial cells as an efficient EV recipient system, in which irradiation of recipient cells further increased the uptake. Furthermore an apoptosis suppressive effect of EVs from irradiated PBMCs in endothelial recipient cells was detected. In summary, this study demonstrates that IR modifies the communication between PBMCs and endothelial cells. EVs from irradiated PBMC donors were identified as transmitters of protective signals to irradiated endothelial cells. Thus, these data may lead to the discovery of biomarker candidates for radiation dosimetry and even more importantly, they suggest EVs as a novel systemic communication pathway between irradiated normal, non-cancer tissues.

Dataset Information

Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early- and late-pubertal males.

Publications

Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early- and late-pubertal males.

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