Role of protein kinase C in TBT-induced inhibition of lytic function and MAPK activation in human natural killer cells
| Autor: | Abraham B. Abraha, Margaret M. Whalen, Krupa Rana |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
MAPK/ERK pathway
Cytotoxicity Immunologic Male Bisindolylmaleimide Health Toxicology and Mutagenesis p38 mitogen-activated protein kinases Toxicology Article Natural killer cell chemistry.chemical_compound medicine Humans Protein kinase C Protein Kinase C biology Kinase General Medicine Cytotoxicity Tests Immunologic Pollution Cell biology Enzyme Activation Killer Cells Natural medicine.anatomical_structure chemistry Biochemistry Lytic cycle Mitogen-activated protein kinase biology.protein Female Mitogen-Activated Protein Kinases Trialkyltin Compounds |
| Zdroj: | Archives of environmental contamination and toxicology. 59(4) |
| ISSN: | 1432-0703 |
| Popis: | Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposures of NK cells to tributyltin (TBT) greatly diminish their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in the NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C (PKC) as well as MAPK activity. The TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to a subsequent encounter with a target cell. In the present study we evaluated the involvement of PKC in the inhibition of NK lysis of tumor cells and activation of MAPKs caused by TBT exposures. TBT caused a 2–3 fold activation of PKC at concentrations ranging from 50–300 nM (16–98 ng/mL), indicating that activation of PKC occurs in response to TBT exposures. This would then leave the NK cell unable to respond to targets. Treatment with the PKC inhibitor, bisindolylmaleimide I, caused an 85% decrease in the ability of NK cells to lyse tumor cells validating the involvement of PKC in the lytic signaling pathway. The role of PKC in the activation of MAPKs by TBT was also investigated using bisindolylmaleimide I. The results indicated that in NK cells where PKC activation was blocked there was no activation of the MAPK, p44/42 in response to TBT. However, TBT-induced activation of the MAPKs, p38 and JNK did not require PKC activation. These results indicate the pivotal role of PKC in the TBT-induced loss of NK lytic function including the activation of p44/42 by TBT in NK cells. |
| Databáze: | OpenAIRE |
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