Tributyltin Effects on Akt/Protein Kinase B and Ribosomal S6 Protein Phosphorylation

다국어 초록 (Multilingual Abstract)

The ERK1/2 and p38 mitogen activated protein kinase (MAPK) pathway have been shown to be activated by exposure to the environmental contaminant tributyltin (TBT). TBT is found to contaminate a number of food products that humans consume resulting in measureable levels in human blood (ranging as high as 261 nM) as well as other tissues. Recent studies have shown that TBT at certain concentrations increases the production of the pro‐inflammatory cytokine interleukin 1 beta (IL‐1β) from human lymphocytes without increasing the mRNA for IL‐1β. TBT‐induced production of IL‐1β appears to require the ERK1/2 and p38 pathways. However, it is possible that TBT may be activating other pathways such as Akt/protein kinase B (PKB) which could also contribute to its ability to increase IL‐1β production. Additionally, downstream substrates of both ERK1/2 and Akt/PKB can lead to the activation of protein synthesis in part by stimulating phosphorylation of the ribosomal S6 protein. Thus, the current study examines whether TBT is able to activate Akt/PKB and S6 phosphorylation as possible mechanisms for the TBT‐induced increases in IL‐1β production. Human lymphocytes were exposed to TBT for 10 minutes. Following the exposure the cells were lysed. The lysates were analyzed using western blot. Antibodies specific to the activated forms of Akt/PKB and S6 were used. Initial results indicate that exposure to TBT increases the activation of Akt/PKB and S6. Thus, it is possible that TBT is stimulating IL‐1β production by activating both MAPK and Akt/PKB signaling pathways leading to increased translation of IL‐1β.
Support or Funding Information
Supported by NIH grant U54CA163066 and 2T34GM007663
This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.