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Title: Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death

Abstract

AMP-activated protein kinase (AMPK), a member of the metabolite-sensing protein kinase family, is activated by energy deficiency and is abundantly expressed in neurons. The environmental pollutant, tributyltin chloride (TBT), is a neurotoxin, and has been reported to decrease cellular ATP in some types of cells. Therefore, we investigated whether TBT activates AMPK, and whether its activation contributes to neuronal cell death, using primary cultures of cortical neurons. Cellular ATP levels were decreased 0.5 h after exposure to 500 nM TBT, and the reduction was time-dependent. It was confirmed that most neurons in our culture system express AMPK, and that TBT induced phosphorylation of AMPK. Compound C, an AMPK inhibitor, reduced the neurotoxicity of TBT, suggesting that AMPK is involved in TBT-induced cell death. Next, the downstream target of AMPK activation was investigated. Nitric oxide synthase, p38 phosphorylation and Akt dephosphorylation were not downstream of TBT-induced AMPK activation because these factors were not affected by compound C, but glutamate release was suggested to be controlled by AMPK. Our results suggest that activation of AMPK by TBT causes neuronal death through mediating glutamate release.

Authors:
 [1];  [1]; ;  [1]
  1. Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553 (Japan)
Publication Date:
OSTI Identifier:
21140914
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 230; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2008.03.021; PII: S0041-008X(08)00137-3; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; ATP; CHLORIDES; DEATH; NERVE CELLS; NITRIC OXIDE; PHOSPHORYLATION; POLLUTANTS; PROTEINS; TIME DEPENDENCE

Citation Formats

Nakatsu, Yusuke, Kotake, Yaichiro, Hino, Atsuko, and Ohta, Shigeru. Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death. United States: N. p., 2008. Web. doi:10.1016/j.taap.2008.03.021.
Nakatsu, Yusuke, Kotake, Yaichiro, Hino, Atsuko, & Ohta, Shigeru. Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death. United States. https://doi.org/10.1016/j.taap.2008.03.021
Nakatsu, Yusuke, Kotake, Yaichiro, Hino, Atsuko, and Ohta, Shigeru. 2008. "Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death". United States. https://doi.org/10.1016/j.taap.2008.03.021.
@article{osti_21140914,
title = {Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death},
author = {Nakatsu, Yusuke and Kotake, Yaichiro and Hino, Atsuko and Ohta, Shigeru},
abstractNote = {AMP-activated protein kinase (AMPK), a member of the metabolite-sensing protein kinase family, is activated by energy deficiency and is abundantly expressed in neurons. The environmental pollutant, tributyltin chloride (TBT), is a neurotoxin, and has been reported to decrease cellular ATP in some types of cells. Therefore, we investigated whether TBT activates AMPK, and whether its activation contributes to neuronal cell death, using primary cultures of cortical neurons. Cellular ATP levels were decreased 0.5 h after exposure to 500 nM TBT, and the reduction was time-dependent. It was confirmed that most neurons in our culture system express AMPK, and that TBT induced phosphorylation of AMPK. Compound C, an AMPK inhibitor, reduced the neurotoxicity of TBT, suggesting that AMPK is involved in TBT-induced cell death. Next, the downstream target of AMPK activation was investigated. Nitric oxide synthase, p38 phosphorylation and Akt dephosphorylation were not downstream of TBT-induced AMPK activation because these factors were not affected by compound C, but glutamate release was suggested to be controlled by AMPK. Our results suggest that activation of AMPK by TBT causes neuronal death through mediating glutamate release.},
doi = {10.1016/j.taap.2008.03.021},
url = {https://www.osti.gov/biblio/21140914}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 230,
place = {United States},
year = {Fri Aug 01 00:00:00 EDT 2008},
month = {Fri Aug 01 00:00:00 EDT 2008}
}