PMID- 20371977 OWN - NLM STAT- MEDLINE DCOM- 20100706 LR - 20211203 IS - 1880-3989 (Electronic) IS - 0388-1350 (Linking) VI - 35 IP - 2 DP - 2010 Apr TI - Involvement of autophagy via mammalian target of rapamycin (mTOR) inhibition in tributyltin-induced neuronal cell death. PG - 245-51 AB - Tributyltin chloride (TBT) is a neurotoxic environmental pollutant that inhibits mitochondrial adenosine triphosphate (ATP) synthase. Autophagy is one of the major protein degradation systems induced by a decrease of intracellular ATP following activation of AMP-activated protein kinase (AMPK). Because we previously found that TBT induces activation of AMPK, here we examined whether TBT induces autophagic neuronal death. Exposure of cortical neurons to 500 nM TBT reduced the phosphorylation of mammalian target of rapamycin (mTOR), a regulator of autophagy. An autophagy inhibitor, 3-methyladenine (3-MA), markedly decreased TBT-induced neuronal death. TBT also induced the formation of LC3-II, an autophagy marker. These results suggest that TBT-induced neuronal death is at least partly autophagic. FAU - Nakatsu, Yusuke AU - Nakatsu Y FAU - Kotake, Yaichiro AU - Kotake Y FAU - Takai, Naoko AU - Takai N FAU - Ohta, Shigeru AU - Ohta S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - J Toxicol Sci JT - The Journal of toxicological sciences JID - 7805798 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (LC3 protein, rat) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Trialkyltin Compounds) RN - 4XDX163P3D (tributyltin) RN - 5142-23-4 (3-methyladenine) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - JAC85A2161 (Adenine) SB - IM MH - AMP-Activated Protein Kinases/physiology MH - Adenine/analogs & derivatives/pharmacology MH - Animals MH - Autophagy/*physiology MH - Cell Death/drug effects MH - Cells, Cultured MH - Female MH - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors MH - Microtubule-Associated Proteins/metabolism MH - Neurons/*drug effects MH - Protein Serine-Threonine Kinases/*antagonists & inhibitors MH - Rats MH - Rats, Wistar MH - TOR Serine-Threonine Kinases MH - Trialkyltin Compounds/*toxicity EDAT- 2010/04/08 06:00 MHDA- 2010/07/07 06:00 CRDT- 2010/04/08 06:00 PHST- 2010/04/08 06:00 [entrez] PHST- 2010/04/08 06:00 [pubmed] PHST- 2010/07/07 06:00 [medline] AID - JST.JSTAGE/jts/35.245 [pii] AID - 10.2131/jts.35.245 [doi] PST - ppublish SO - J Toxicol Sci. 2010 Apr;35(2):245-51. doi: 10.2131/jts.35.245.