title: 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. One hour 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.
authors.affiliation: Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Person
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Whalen
mesh_terms: D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D009947:Organotin Compounds / Q000633:toxicity*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014220:Trialkyltin Compounds / Q000633:toxicity*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism*
chemical_list: D016761:Oncogene Proteins v-fos; D009947:Organotin Compounds; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014220:Trialkyltin Compounds; D050807:ets-Domain Protein Elk-1; C056189:di-n-butyltin; C011559:tributyltin; D020928:Mitogen-Activated Protein Kinases