PMID- 18989867
OWN - NLM
STAT- MEDLINE
DCOM- 20090728
LR  - 20181113
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Print)
IS  - 0260-437X (Linking)
VI  - 29
IP  - 2
DP  - 2009 Mar
TI  - The role of p44/42 activation in tributyltin-induced inhibition of human natural 
      killer cells: effects of MEK inhibitors.
PG  - 165-73
LID - 10.1002/jat.1397 [doi]
AB  - Destruction of tumor cells is a key function of natural killer (NK) cells. 
      Previous studies have shown that tributyltin (TBT) can significantly reduce the 
      lytic function of the human NK cells with accompanying increases in the 
      phosphorylation (activation) states of the mitogen activated protein kinases 
      (MAPKs), p44/42. The current studies examine the role of p44/42 activation in the 
      TBT-induced reduction of NK-lytic function, by using MAPK kinase (MEK) 
      inhibitors, PD98059 and U0126. A 1 h treatment with PD98059 or U0126 or both 
      decreased the ability of NK cells to lyse K562 tumor cells. PD98059, U0126 or a 
      combination of both inhibitors were able to completely block TBT-induced 
      activation of p44/42. However, when p44/42 activation was blocked by the presence 
      of PD98059, U0126 or the combination, subsequent exposure to TBT was still able 
      to decrease the lytic function of NK cells. These results indicate that 
      TBT-induced activation of p44/42 occurs via the activation of its upstream 
      activator, MEK, and not by a TBT-induced inhibition of p44/42 phosphatase 
      activity. Additionally, as lytic function was never completely blocked by MEK 
      inhibitors, the results indicate that activation of p44/42 pathway is not solely 
      responsible for the activation of lytic function of freshly isolated human NK 
      cells. Finally, the results showed that TBT-induced activation of p44/42 is not 
      solely responsible for the loss of lytic function.
FAU - Abraha, Abraham B
AU  - Abraha AB
AD  - Department of Chemistry, Tennessee State University, Nashville, TN 37209-1561, 
      USA.
FAU - Whalen, Margaret M
AU  - Whalen MM
LA  - eng
GR  - S06 GM008092/GM/NIGMS NIH HHS/United States
GR  - S06 GM008092-320003/GM/NIGMS NIH HHS/United States
GR  - 2S06GM-08092-32/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Butadienes)
RN  - 0 (Cell Extracts)
RN  - 0 (Drug Combinations)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Nitriles)
RN  - 0 (Trialkyltin Compounds)
RN  - 0 (U 0126)
RN  - 4XDX163P3D (tributyltin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.1.3.16 (Mitogen-Activated Protein Kinase Phosphatases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Butadienes/pharmacology
MH  - Cell Extracts
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - K562 Cells
MH  - Killer Cells, Natural/*drug effects/immunology/metabolism
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase Phosphatases/analysis/metabolism
MH  - Nitriles/pharmacology
MH  - Phosphorylation/drug effects
MH  - Time Factors
MH  - Trialkyltin Compounds/*toxicity
PMC - PMC2642538
MID - NIHMS75540
EDAT- 2008/11/08 09:00
MHDA- 2009/07/29 09:00
PMCR- 2010/03/01
CRDT- 2008/11/08 09:00
PHST- 2008/11/08 09:00 [pubmed]
PHST- 2009/07/29 09:00 [medline]
PHST- 2008/11/08 09:00 [entrez]
PHST- 2010/03/01 00:00 [pmc-release]
AID - 10.1002/jat.1397 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2009 Mar;29(2):165-73. doi: 10.1002/jat.1397.