The FA mixture also promoted an increase in intracellular Ca2+ mo

The FA mixture also promoted an increase in intracellular Ca2+ mobilization and in the proliferative capacity of B-lymphocytes. Treatment of cells with the antioxidant ASTA partially decreased the oxidative stress imposed by the FA mixture. Ca2+ signaling is essential for diverse biological processes. Ca2+ ions are especially

suited as intracellular second messengers because of the strong homeostatic mechanisms that maintain intracellular Enzalutamide cell line free Ca2+ concentrations ([Ca2+]i) in resting cells at 100 nM or less. In the face of extracellular Ca2+ concentrations ([Ca2+]o) that are four orders of magnitude higher (1–2 mM). Cytoplasmic Ca2+ concentrations are maintained at low levels primarily through the action of plasma membrane Ca2+-ATPases (PMCAs) that pump Ca2+ out of the cell across the plasma membrane. Additionally, the sarco-endoplasmic reticulum Ca2+-ATPases (SERCAs) pumps Ca2+ into the lumen of the endoplasmic reticulum (ER). In the longer term (hours), Birinapant chemical structure sustained Ca2+ entry is critical for essentially all responses initiated through T cell, B cell, and Fc receptors, including proliferation and cytokine production by T cells, cytokine production by mast cells and natural killer (NK) cells, differentiation of B cells into plasma cells, and the differentiation of naive T cells into Th1,

Th2, and Th17 effectors subtypes (Hogan et al., 2010). As showed in our work, intracellular calcium concentration was exceptionally enhanced and sustained during 20 min of monitoring in cells treated with FA mixture (Fig. 2) and addition of ASTA to FA-treated cells was unable to restore calcium to basal Doxorubicin levels. At the same time, proliferative capacity of lymphocytes

was increased by the presence of FA mixture, and ASTA addition restored proliferative capacity of lymphocytes to control values (Fig. 1). Based on this data we are able to suggest that proliferative response of lymphocytes, which is a well-known calcium-dependent process is not the only mechanism involved in this process since ASTA decreased proliferative capacity of cells treated with FA but did not reduce intracellular calcium concentration. It has been shown that ASTA is a potent inhibitor of tyrosine kinases, inhibiting the MAPK pathway, decreasing the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPK and MEK pathway, down regulating the NF-κB activation and ERK1/2 and pMSK-1 pathway (Lee et al., 2003 and Kim et al., 2010). Whether ASTA is reducing lymphocyte proliferation by inhibiting the phosphorylation of key proteins implicated in the process of lymphocyte proliferation remains to be elucidated.

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