Dataset Information

Beep Test Does Not Induce Phosphorylation of Ras/MAPK- or JAK/STAT-Related Proteins in Peripheral Blood T Lymphocytes.

ABSTRACT: The Th1 cell subset is involved in the immunological response induced by physical exercise. The aim of this work is to evaluate the post-effort activation of Ras/MAPK and JAK/STAT signaling pathways in T cells of young, physically active men. Seventy-six physically active, healthy men between 15 and 21 years old performed a standard physical exercise protocol (Beep test). Phosphorylation levels of Ras/MAPK-(p38 MAPK, ERK1/2) and JAK/STAT-related (STAT1, STAT3, STAT5, and STAT6) proteins were evaluated by flow cytometry in Th and Tc cells post-effort and during the lactate recovery period. The performed physical effort was not a strong enough physiological stimulant to provoke the phosphorylation of ERK1/2, p38 MAPK, STAT1, STAT3, STAT5, and STAT6 in T cells, at least for the duration of our study (the end of the lactate recovery period). We conclude that more observation time-points, including shorter and longer times after the exercise, are required to determine if the Ras/MAPK signaling pathway is involved in modulating the post-effort immunological response.

SUBMITTER: Kostrzewa-Nowak D

PROVIDER: S-EPMC8965037 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Beep Test Does Not Induce Phosphorylation of Ras/MAPK- or JAK/STAT-Related Proteins in Peripheral Blood T Lymphocytes.

Kostrzewa-Nowak Dorota D Nowak Robert R

Frontiers in physiology 20220315

The Th1 cell subset is involved in the immunological response induced by physical exercise. The aim of this work is to evaluate the post-effort activation of Ras/MAPK and JAK/STAT signaling pathways in T cells of young, physically active men. Seventy-six physically active, healthy men between 15 and 21 years old performed a standard physical exercise protocol (Beep test). Phosphorylation levels of Ras/MAPK-(p38 MAPK, ERK1/2) and JAK/STAT-related (STAT1, STAT3, STAT5, and STAT6) proteins were eva ...[more]

PMID: 35370792

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Project description:Background and objectivesIgA nephropathy is the most common primary glomerular disease in the world. Marked by mesangial inflammation and proliferation, it generally leads to progressive kidney fibrosis. As the Janus kinase signal transducer and activator of transcription pathway has been implicated as an important mediator of diabetic kidney disease and FSGS, detailed investigation of this pathway in IgA nephropathy was undertaken to establish the basis for targeting this pathway across glomerular diseases.Design, setting, participants, & measurementsWell characterized patients with IgA nephropathy and controls were studied, allowing us to compare 77 patients with biopsy-proven IgA nephropathy with 45 healthy subjects. STAT phosphorylation was assessed in peripheral blood monocytes (PBMCs) by phosphoflow before and after cytokine stimulation. Kidney Janus kinase signal transducer and activator of transcription activity was studied by immunofluorescence and by transcriptomic studies. An STAT1 activity score was established using downstream transcriptional targets of pSTAT1 and associated with disease and clinical outcomes.ResultsWe found PBMCs to have upregulated pSTAT production at baseline in patients with IgA nephropathy with a limited reserve to respond to cytokine stimulation compared with controls. Increased staining in glomerular mesangium and endothelium was seen for Jak-2 and pSTAT1 and in the tubulointerstitial for JAK2, pSTAT1, and pSTAT3. Activation of the Janus kinase signal transducer and activator of transcription pathway was further supported by increased pSTAT1 and pSTAT3 scores in glomerular and tubulointerstitial sections of the kidney (glomerular activation Z scores: 7.1 and 4.5, respectively; P values: <0.001 and <0.001, respectively). Clinically, phosphoflow results associated with proteinuria and kidney function, and STAT1 activation associated with proteinuria but was not associated with progression.ConclusionsJanus kinase signal transducer and activator of transcription signaling was activated in patients with IgA nephropathy compared with controls. There were altered responses in peripheral immune cells and increased message and activated proteins in the kidney. These changes variably related to proteinuria and kidney function.

Project description:A metabolite isolated from fermented soybean, 8-hydroxydaidzein (8-OHD, 7,8,4'-trihydroxyisoflavone, NSC-678112), is widely used in ethnopharmacological research due to its anti-proliferative and anti-inflammatory effects. We reported previously that 8-OHD provoked reactive oxygen species (ROS) overproduction, and induced autophagy, apoptosis, breakpoint cluster region-Abelson murine leukemia viral oncogene (BCR-ABL) degradation, and differentiation in K562 human chronic myeloid leukemia (CML) cells. However, how 8-OHD regulates metabolism, the extracellular matrix during invasion and metastasis, and survival signaling pathways in CML remains largely unexplored. High-throughput technologies have been widely used to discover the therapeutic targets and pathways of drugs. Bioinformatics analysis of 8-OHD-downregulated differentially expressed genes (DEGs) revealed that Janus kinase/signal transducer and activator of transcription (JAK/STAT), matrix metalloproteinases (MMPs), c-Myc, phosphoinositide 3-kinase (PI3K)/AKT, and oxidative phosphorylation (OXPHOS) metabolic pathways were significantly altered by 8-OHD treatment. Western blot analyses validated that 8-OHD significantly downregulated cytosolic JAK2 and the expression and phosphorylation of STAT3 dose- and time-dependently in K562 cells. Zymography and transwell assays also confirmed that K562-secreted MMP9 and invasion activities were dose-dependently inhibited by 8-OHD after 24 h of treatment. RT-qPCR analyses verified that 8-OHD repressed metastasis and OXPHOS-related genes. In combination with DisGeNET, it was found that 8-OHD's downregulation of PI3K/AKT is crucial for controlling CML development. A STRING protein-protein interaction analysis further revealed that AKT and MYC are hub proteins for cancer progression. Western blotting revealed that AKT phosphorylation and nuclear MYC expression were significantly inhibited by 8-OHD. Collectively, this systematic investigation revealed that 8-OHD exerts anti-CML effects by downregulating JAK/STAT, PI3K/AKT, MMP, and OXPHOS pathways, and MYC expression. These results could shed new light on the development of 8-OHD for CML therapy.

Dataset Information

Beep Test Does Not Induce Phosphorylation of Ras/MAPK- or JAK/STAT-Related Proteins in Peripheral Blood T Lymphocytes.

Publications

Beep Test Does Not Induce Phosphorylation of Ras/MAPK- or JAK/STAT-Related Proteins in Peripheral Blood T Lymphocytes.

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