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08:49
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Ouabain inhibits p38 activation in thymocytes
Sandra Rodrigues-Mascarenhas1, Flavia Fonseca Bloise, Jorge Moscat
1Laboratório de Tecnologia Farmacêutica, Departamento de Fisiologia e Patologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil. sandramascarenhas@ccs.ufpb.br
Cell Biology International
|August 16, 2008
Summary
Ouabain, a Na+/K+-ATPase inhibitor, was found to suppress the activation of p38 (a key signaling protein) and NFATc1 (a transcription factor) in T-cells. This suggests ouabain impacts an alternative signaling pathway crucial for immune cell activation.
Area of Science:
- Immunology
- Cell Signaling
- Molecular Biology
Background:
- Mitogen-activated protein kinase (MAPK) p38 is activated by various stimuli and regulates transcription factors.
- p38 activation, particularly its regulation of Nuclear Factor of Activated T-cells (NFAT), may involve a MKK-independent pathway.
- This alternative pathway utilizes Dlgh1 as a scaffold protein for p38 activation.
Purpose of the Study:
- To investigate the effect of ouabain, a Na+/K+-ATPase inhibitor, on p38 phosphorylation and NFATc1 expression in Concanavalin A (ConA)-activated thymocytes.
- To explore the potential role of ouabain in modulating the MKK-independent p38 activation pathway.
Main Methods:
- Primary thymocytes were activated using Concanavalin A (ConA).
- Cells were treated with varying concentrations of ouabain (1, 10, and 100 nM).
- Phosphorylated p38 (P-p38) levels and NFATc1 expression were quantified using flow cytometry.
Main Results:
- Ouabain treatment significantly inhibited the ConA-induced increase in P-p38 levels.
- Ouabain also suppressed the ConA-dependent elevation of NFATc1 expression.
- These findings indicate that ouabain affects the signaling cascade leading to p38 activation.
Conclusions:
- Ouabain inhibits p38 phosphorylation and NFATc1 expression in activated thymocytes.
- The results suggest that ouabain interferes with the MKK-independent p38 activation pathway.
- This study highlights a novel regulatory role for ouabain in T-cell signaling.
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