Akt/mammalian target of rapamycin signaling pathway regulates neurite outgrowth in cerebellar granule neurons stimulated by methylcobalamin

被引:37
作者
Okada, Kiyoshi [1 ,2 ]
Tanaka, Hiroyuki [3 ]
Temporin, Ko [4 ]
Okamoto, Michio [1 ]
Kuroda, Yusuke [1 ]
Moritomo, Hisao [1 ]
Murase, Tsuyoshi [1 ]
Yoshikawa, Hideki [1 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Orthopaed, Suita, Osaka 5650871, Japan
[2] Osaka Univ Hosp, Med Ctr Translat Res, Suita, Osaka 5650871, Japan
[3] Osaka Koseinenkin Hosp, Dept Orthopaed Surg, Osaka 5530003, Japan
[4] Toyonaka City Hosp, Dept Orthopaed Surg, Toyonaka, Osaka 5608566, Japan
关键词
Akt; Mammalian target or rapamycin; Methylcobalamin; Neurite outgrowth; PROMOTES NERVE REGENERATION; HIGH-DOSE METHYLCOBALAMIN; MAMMALIAN TARGET; DNA METHYLATION; SCIATIC-NERVE; AKT; MTOR; KINASE; GROWTH; RAF;
D O I
10.1016/j.neulet.2011.03.065
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:201 / 204
页数:4
相关论文
共 35 条
[1]   Mammalian Target of Rapamycin (mTOR) Activation Increases Axonal Growth Capacity of Injured Peripheral Nerves [J].
Abe, Namiko ;
Borson, Steven H. ;
Gambello, Michael J. ;
Wang, Fan ;
Cavalli, Valeria .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (36) :28034-28043
[2]  
AKAIKE A, 1993, EUR J PHARMACOL, V241, P1
[3]   Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf [J].
Bergo, MO ;
Gavino, BJ ;
Hong, C ;
Beigneux, AP ;
McMahon, M ;
Casey, PJ ;
Young, SG .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (04) :539-550
[4]   S-Adenosylmethionine and protein methylation [J].
Grillo, MA ;
Colombatto, S .
AMINO ACIDS, 2005, 28 (04) :357-362
[5]   3-(Hydroxymethyl)-bearing phosphatidylinositol ether lipid analogues and carbonate surrogates block PI3-K, Akt, and cancer cell growth [J].
Hu, YH ;
Qiao, LX ;
Wang, SM ;
Rong, SB ;
Meuillet, EJ ;
Berggren, M ;
Gallegos, A ;
Powis, G ;
Kozikowski, AP .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (16) :3045-3051
[6]   Rapamycins - Mechanism of action and cellular resistance [J].
Huang, SL ;
Bjornsti, MA ;
Houghton, PJ .
CANCER BIOLOGY & THERAPY, 2003, 2 (03) :222-232
[7]  
Izumi Yuishin, 2007, Brain and Nerve (Tokyo), V59, P1141
[8]  
JALALUDIN MA, 1995, METHOD FIND EXP CLIN, V17, P539
[9]   The growing role of mTOR in neuronal development and plasticity [J].
Jaworski, Jacek ;
Sheng, Morgan .
MOLECULAR NEUROBIOLOGY, 2006, 34 (03) :205-219
[10]  
Kikuchi M, 1997, INVEST OPHTH VIS SCI, V38, P848