PMID- 21458538 OWN - NLM STAT- MEDLINE DCOM- 20110826 LR - 20211203 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 495 IP - 3 DP - 2011 May 20 TI - Akt/mammalian target of rapamycin signaling pathway regulates neurite outgrowth in cerebellar granule neurons stimulated by methylcobalamin. PG - 201-4 LID - 10.1016/j.neulet.2011.03.065 [doi] AB - Methylcobalamin (MeCbl), a vitamin B12 analog, promotes neurite outgrowth by activating Akt in neurons. However, Akt is involved in many cellular functions, and the downstream signal of Akt that promotes neurite outgrowth in neurons in the presence of MeCbl remains obscure. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates multiple cellular functions including neurite outgrowth. mTOR is regarded as important for the regeneration of injured nerves. In this study, we examined the relationship between MeCbl and mTOR activity and found that MeCbl increases mTOR activity via the activation of Akt and promotes neurite outgrowth in cerebellar granule neurons via the activation of mTOR. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Okada, Kiyoshi AU - Okada K AD - Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kokada2433@snow.ocn.ne.jp FAU - Tanaka, Hiroyuki AU - Tanaka H FAU - Temporin, Ko AU - Temporin K FAU - Okamoto, Michio AU - Okamoto M FAU - Kuroda, Yusuke AU - Kuroda Y FAU - Moritomo, Hisao AU - Moritomo H FAU - Murase, Tsuyoshi AU - Murase T FAU - Yoshikawa, Hideki AU - Yoshikawa H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110330 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Morpholines) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - BR1SN1JS2W (mecobalamin) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - P6YC3EG204 (Vitamin B 12) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Cells, Cultured MH - Cerebellum/*cytology MH - Chromones/pharmacology MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation/drug effects MH - Morpholines/pharmacology MH - Neurites/*drug effects MH - Neurons/*cytology/drug effects MH - Oncogene Protein v-akt/*metabolism MH - Rats MH - Rats, Wistar MH - Signal Transduction/*drug effects MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/*metabolism MH - Vitamin B 12/*analogs & derivatives/pharmacology EDAT- 2011/04/05 06:00 MHDA- 2011/08/30 06:00 CRDT- 2011/04/05 06:00 PHST- 2010/12/24 00:00 [received] PHST- 2011/03/15 00:00 [revised] PHST- 2011/03/21 00:00 [accepted] PHST- 2011/04/05 06:00 [entrez] PHST- 2011/04/05 06:00 [pubmed] PHST- 2011/08/30 06:00 [medline] AID - S0304-3940(11)00379-X [pii] AID - 10.1016/j.neulet.2011.03.065 [doi] PST - ppublish SO - Neurosci Lett. 2011 May 20;495(3):201-4. doi: 10.1016/j.neulet.2011.03.065. Epub 2011 Mar 30.