PMID- 19734680 OWN - NLM STAT- MEDLINE DCOM- 20091231 LR - 20211203 IS - 1347-6947 (Electronic) IS - 0916-8451 (Linking) VI - 73 IP - 9 DP - 2009 Sep TI - Ethionine-induced ATP depletion represses mTOR signaling in the absence of increases in AMP-activated protein kinase activity in the rat liver. PG - 1984-8 AB - Administration of ethionine to female rats caused a rapid and severe decline in liver ATP and inhibited hepatic protein synthesis in association with hypophosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and 70-kDa ribosomal protein S6 kinase (S6K1), two key regulatory proteins involved in initiation of mRNA translation. Phosphorylation of both regulatory proteins is mediated through a signaling pathway that involves the mammalian target of rapamycin (mTOR). Recent studies indicate that AMP-activated protein kinase (AMPK) plays a role in the cellular response to environmental stresses, which deplete ATP, and suppresses protein synthesis through downregulated mTOR signaling. We investigated the possible involvement of AMPK in the ethionine-induced inhibition of protein synthesis. The administration of ethionine surprisingly decreased AMPK activity compared with controls despite ATP depletion. We conclude that inhibition of protein synthesis by ethionine is due to AMPK-independent inhibition of mTOR signaling following ATP depletion. FAU - Yoshizawa, Fumiaki AU - Yoshizawa F AD - Department of Animal Science, Utsunomiya University, Utsunomiya, Tochigi 321-8205, Japan. fumiaki@cc.utsunomiya-u.ac.jp FAU - Mochizuki, Shinji AU - Mochizuki S FAU - Doi, Masako AU - Doi M FAU - Yamaoka, Ippei AU - Yamaoka I FAU - Sugahara, Kunio AU - Sugahara K LA - eng PT - Journal Article DEP - 20090907 PL - England TA - Biosci Biotechnol Biochem JT - Bioscience, biotechnology, and biochemistry JID - 9205717 RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - WX1BN24WZT (Ethionine) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Adenosine Triphosphate/*metabolism MH - Animals MH - Chromatography, High Pressure Liquid MH - Ethionine/*pharmacology MH - Female MH - Liver/*drug effects/enzymology MH - Phosphorylation MH - Protein Kinases/*metabolism MH - Rats MH - Rats, Wistar MH - Signal Transduction/*drug effects MH - TOR Serine-Threonine Kinases EDAT- 2009/09/08 06:00 MHDA- 2010/01/01 06:00 CRDT- 2009/09/08 06:00 PHST- 2009/09/08 06:00 [entrez] PHST- 2009/09/08 06:00 [pubmed] PHST- 2010/01/01 06:00 [medline] AID - JST.JSTAGE/bbb/90154 [pii] AID - 10.1271/bbb.90154 [doi] PST - ppublish SO - Biosci Biotechnol Biochem. 2009 Sep;73(9):1984-8. doi: 10.1271/bbb.90154. Epub 2009 Sep 7.