Effects of butyltins on cytosolic calcium ion levels, MAPKs signaling pathways and apoptotic pathways in human natural killer cells
Natural killer (NK) cells are lymphocytes that kill tumor cells, virally infected cells and antibody coated cells. Butyltins (BTs) are used in industrial, agricultural and consumer applications and contaminate the global environment. Tributyltin (TBT) has been used for wood preservation, disinfection, antifouling marine paints, and slime control in paper mills. Dibutyltin (DBT) has been used as a stabilizer in polyvinyl chloride (PVC) plastic products. BTs inhibit the cytotoxic function of NK cells and have been found in human blood. Exposures of NK cells to TBT caused significant decreases in cytotoxic function coupled with activation (phosphorylation) of mitogen-activated protein kinases (MAPKs). TBT also caused an increase in cytosolic Ca2+. The hypothesis being tested in the current study is that DBT causes increases in cytosolic Ca2+ and activation of MAPKS DBT caused small but significant increases in Ca2+cyt after 30 and 60 min. The increases were 20% above control for 10 μM DBT and 13% for 5 μM DBT. Ten minute exposures to DBT activated the MAPK, p38 at every concentration tested. Activation was accompanied by an activation of the enzyme that activates p38, the MAP2K, MKK3/6. Exposure to DBT for 10 min also activated p44/42 and its MAP2K, MEK1/2, at the two highest concentrations of DBT. One hour exposures to DBT activated p38 and MKK3/6 at all concentration (10, 5, 2.5, 1μM) except for the lowest DBT concentration (0.5μM), A 6 hour exposure to DBT induced significant activation of p38 and MKK3/6 at the 10 μM concentration. After a 6 h exposure to 10 μM DBT there was also a very significant activation of p44/42. Thus, the ability of DBT to activate p38 diminished with length of exposure, similar to what was seen when NK cells were exposed to TBT. The effect of TBT and DBT on the Caspase-3 activity and XIAP enzyme was also assessed in this study, no significant changes were observed when the NK cells were exposed to 300, 200, 100, 50 and 25 nM TBT and 10, 5, 2.5, 1, 0.5 μM DBT for 10 min, 60 min and 24 h.^
Biology, Molecular|Biology, Cell
Sabah O Odman-Ghazi,
"Effects of butyltins on cytosolic calcium ion levels, MAPKs signaling pathways and apoptotic pathways in human natural killer cells"
ETD Collection for Tennessee State University.