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Decreased integrity of exercise-induced plasma cell free nuclear DNA - negative association with the increased oxidants production by circulating phagocytes.

ABSTRACT: Strenuous exercise increases circulating cell free DNA (cfDNA) and stimulates blood phagocytes to generate reactive oxygen species (ROS) which may induce DNA strand breaks. We tested whether: (A) elevated cfDNA in response to three repeated bouts of exhaustive exercise has decreased integrity; (B) each bout of exercise increases luminol enhanced whole blood chemiluminescence (LBCL) as a measure of ROS production by polymorphonuclear leukocytes. Eleven men performed three treadmill exercise tests to exhaustion separated by 72?hours of resting. Pre- and post-exercise concentrations and integrity of cf nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) and resting (r) and fMLP (n-formyl-methionyl-leucyl-phenylalanine)-stimulated LBCL were determined. Each bout increased concentrations of cf n-DNA by more than 10-times which was accompanied by about 2-times elevated post-exercise rLBCL and fMLP-LBCL. Post-exercise cf n-DNA integrity (integrity index, I229/97) decreased after the first (0.59?±?0.19 vs. 0.48?±?0.18) and second (0.53?±?0.14 vs. 0.44?±?0.17) bout of exercise. There were negative correlations between I229/97 and rLBCL (??=?-0.37), and I229/97 and fMLP-LBCL (??=?-0.40) - analysis of pooled pre- and post-exercise data (n?=?66). cf mt- DNA integrity (I218/78) did not alter in response to exercise. This suggests an involvement of phagocyte ROS in cf n-DNA strand breaks in response to exhaustive exercise.

SUBMITTER: Stawski R

PROVIDER: S-EPMC6828751 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Decreased integrity of exercise-induced plasma cell free nuclear DNA - negative association with the increased oxidants production by circulating phagocytes.

Stawski Robert R Walczak Konrad K Perdas Ewelina E Wlodarczyk Anna A Sarniak Agata A Kosielski Piotr P Meissner Pawel P Budlewski Tomasz T Padula Gianluca G Nowak Dariusz D

Scientific reports 20191104 1

Strenuous exercise increases circulating cell free DNA (cfDNA) and stimulates blood phagocytes to generate reactive oxygen species (ROS) which may induce DNA strand breaks. We tested whether: (A) elevated cfDNA in response to three repeated bouts of exhaustive exercise has decreased integrity; (B) each bout of exercise increases luminol enhanced whole blood chemiluminescence (LBCL) as a measure of ROS production by polymorphonuclear leukocytes. Eleven men performed three treadmill exercise tests ...[more]

PMID: 31685910

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Project description:ObjectiveColorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis.MethodsWe collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis.ResultsThe cytokine response in peripheral CD4+ T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified.ConclusionWe comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells' function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development.

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Decreased integrity of exercise-induced plasma cell free nuclear DNA - negative association with the increased oxidants production by circulating phagocytes.

Publications

Decreased integrity of exercise-induced plasma cell free nuclear DNA - negative association with the increased oxidants production by circulating phagocytes.

Similar Datasets

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