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Modulation of the Immune System by Ouabain
Author(s) -
RodriguesMascarenhas Sandra,
De Oliveira Andreia Da Silva,
Amoedo Nívea Dias,
AffonsoMitidieri Ottilia R.,
Rumjanek Franklin D.,
Rumjanek Vivian M.
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2008.03969.x
Subject(s) - ouabain , microbiology and biotechnology , chemistry , signal transduction , phosphorylation , biology , medicine , sodium , organic chemistry
Ouabain, a known inhibitor of the Na,K‐ATPase, has been shown to regulate a number of lymphocyte functions in vitro and in vivo . Lymphocyte proliferation, apoptosis, cytokine production, and monocyte function are all affected by ouabain. The ouabain‐binding site occurs at the α subunit of the enzyme. The α subunit plays a critical role in the transport process, and four different α‐subunit isoforms have been described with different sensitivities to ouabain. Analysis by RT‐PCR indicates that α1, α2, and α3 isoforms are all present in murine lymphoid cells obtained from thymus, lymph nodes, and spleen. In these cells ouabain exerts an effect at concentrations that do not induce plasma membrane depolarization, suggesting a mechanism independent of the classical inhibition of the pump. In other systems, the Na,K‐ATPase acts as a signal transducer in addition to being an ion pump, and ouabain is capable of inducing the activation of various signal transduction cascades. Neither resting nor concanavalin A (Con A)‐activated thymocytes had their levels of phosphorylated‐extracellular signal‐regulated kinase (P‐ERK) modified by ouabain. However, ouabain decreased p38 phosphorylation induced by Con A in these cells. The pathway induced by ouabain in lymphoid cells is still unclear but might vary with the type and state of activation of the cell.