Effects of butyltin exposures on MAP kinase-dependent transcription regulators in human natural killer cells

Abstract

Natural Killer (NK) cells are a major immune defense mechanism against cancer development and viral infection. The butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) have been widely used in industrial and other applications and significantly contaminate the environment. Both TBT and DBT have been detected in human blood. These compounds inhibit the lytic and binding function of human NK cells and thus could increase the incidence of cancer and viral infections. Butyltin (BT)-induced loss of NK function is accompanied by activation of mitogen activated protein kinases (MAPKs) and decreases in expression of cell-surface and cytolytic proteins. MAPKs activate components of the transcription regulator AP-1 and activate the transcription regulator Elk-1. Based on the fact that BTs activate MAPKs and alter protein expression, the current study examined the effect of BT exposures on the levels and phosphorylation states of the components of AP-1 and the phosphorylation state of Elk-1. Exposure to 300 nM TBT for 10 min increased the phosphorylation of c-Jun in NK cells. 1 h exposures to 300 nM and 200 nM TBT increased the phosphorylation and overall level of c-Jun. During a 300 nM treatment with TBT for 1 h the binding activity of AP-1 was significantly decreased. There were no significant alterations of AP-1 components or of Elk-1 with DBT exposures. Thus, it appears that TBT-induced alterations on phosphorylation, total levels and binding activity of c-Jun might contribute to, but are not fully responsible for, TBT-induced alterations of NK protein expression.

The effect of environmental chemicals on the tumor microenvironment

“…Butyltins, and specifically TBT, an endocrine disruptor, have been found to inhibit the cytotoxic activity of NK cells (269). This effect is accompanied by the activation of the MAPK pathway, which allows the cell to evade growth control (270). This result is confirmed by other studies showing the downregulation by TBT oxide of MAPKs and other proteins, such as matrin-3 and ribonucleotide reductase, subunit RRM2, which are implicated in cell proliferation (274).…”

Activation of protein kinase C and protein kinase D in human natural killer cells: effects of tributyltin, dibutyltin, and tetrabromobisphenol A

“…TBT also increases the activity of aromatase (estrogen synthetase) (Nakanishi et al, 2002), while DBT has been shown to decrease ligand binding to the glucocorticoid receptor (Gumy et al, 2008). Additionally, TBT increases the phosphorylation and total of levels of the c-Jun component of the AP-1 transcription regulator (Person and Whalen, 2010). Thus, each of these compounds affects the status of transcriptional regulators.…”

Ladder-like Organostannoxane: Synthesis and Crystal Structure of the Second Polymorph {[(C6H5)2Sn]2[(C6H5)2ClSn]2(μ3-O)2(μ2-OH)2}∙[DMF]2

“…Coordination polymers, isolated from an appropriate reaction of selected metal centers and multidirectional ligands, aroused an intriguing interest to researchers due to the potential applications as well the fascinating structures they display [1][2][3][4][5][6][7][8][9]. Organotin(IV) carboxylate based complexes and derivatives have been widely investigated because they are a class of compounds affording very interesting topologies, and a variety of structural types such tetramers and oligomeric ladders [10][11][12].…”