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Issue 5, 2013
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AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells

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Abstract

Organotin compounds such as tributyltin (TBT) are known to cause various forms of cytotoxicity, including developmental toxicity and neurotoxicity. However, the molecular target of the toxicity induced by nanomolar levels of TBT has not been identified. In the present study, we found that exposure to 100 nM TBT induced growth arrest in human pluripotent embryonic carcinoma cell line NT2/D1. Since glucose provides metabolic energy, we focused on the glycolytic system. We found that exposure to TBT reduced the levels of both glucose-6-phosphate and fructose-6-phosphate. To investigate the effect of TBT exposure on glycolysis, we examined glucose transporter (GLUT) activity. TBT exposure inhibited glucose uptake via a decrease in the level of cell surface-bound GLUT1. Furthermore, we examined the effect of AMP-activated protein kinase (AMPK), which is known to regulate glucose transport by facilitating GLUT translocation. Treatment with the potent AMPK activator, AICAR, restored the TBT-induced reduction in cell surface-bound GLUT1 and glucose uptake. In conclusion, these results suggest that exposure to nanomolar levels of TBT causes growth arrest by targeting glycolytic systems in human embryonic carcinoma cells. Thus, understanding the energy metabolism may provide new insights into the mechanisms of metal-induced cytotoxicity.

Graphical abstract: AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells

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Publication details

The article was received on 28 Dec 2012, accepted on 20 Feb 2013 and first published on 22 Feb 2013


Article type: Paper
DOI: 10.1039/C3MT20268B
Metallomics, 2013,5, 484-491

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    AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells

    S. Yamada, Y. Kotake, Y. Sekino and Y. Kanda, Metallomics, 2013, 5, 484
    DOI: 10.1039/C3MT20268B

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