The promotive effects of thymosin β4 on neuronal survival and neurite outgrowth by upregulating L1 expression

被引:64
作者
Yang, Hao [1 ]
Cheng, Xipeng [1 ]
Yao, Qing [1 ]
Li, Jingwen [1 ]
Ju, Gong [1 ]
机构
[1] Fourth Mil Med Univ, Inst Neurosci, Xian 710032, Shaanxi, Peoples R China
关键词
thymosin-beta; 4; L1; neurite outgrowth; survival; immunofluorescene staining; cell culture;
D O I
10.1007/s11064-008-9712-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thymosin beta(4) (T beta 4) is a major actin-sequestering peptide widely distributed in mammalian tissues including the nervous system. The presence of this peptide in the nervous system likely plays a role in synaptogensis, axon growth, cell migration, and plastic changes in dendritic spine. However, the effects of T beta 4 on the survival of neurons and axonal outgrowth have still not been fully understood. So far it is not clear if the effects of T beta 4 are associated with L1 functions. In the present study, we hypothesized that T beta 4-induced up-regulation of L1 synthesis could be involved in the survival and axon outgrowth of cultured spinal cord neurons. To test this hypothesis, primarily cultured neurons were prepared from the mouse spinal cord and treated with various concentrations of T beta 4 ranging from 0.1 to 10 mu g/ml. The analysis of L1 mRNA expression and protein synthesis in neurons was then carried out using RT-PCR and western blot assays, respectively. After the addition of T beta 4 to cultures, cells were then treated with antibodies against distinct domains of L1-Fc. Subsequently, beta-tubulin III and L1 double-labeled indirect immunofluorescence was carried out. Meanwhile, L1 immunofluorescent reactivity was analyzed and compared in cells treated with T beta 4. Furthermore, the number of beta-tubulin III-positive cells and neurite lengths were measured. We found that T beta 4 enhanced L1 expression in a dose-dependent manner, and the highest L1 mRNA and protein synthesis in cells increased by more than 2.1- and 2.3-fold in the presence of T beta 4 at identical concentrations, respectively. Moreover, it also dose dependently enhanced neurite outgrowth and neuronal survival. Compared to conditions without T beta 4, the length of neurite and neuronal survival increased markedly in presence of 0.5, 1, and 5 mu g/ml T beta 4, respectively, whereas the effects of T beta 4 were significantly attenuated or inhibited in the process of L1-Fc antibodies treatment. These above results indicate that the promotive effect of T beta 4 on the survival and neurite outgrowth of cultured spinal cord neurons might be mediated, at least in part via a stimulation of the production of L1 in the neurons.
引用
收藏
页码:2269 / 2280
页数:12
相关论文
共 68 条
[1]   EARLY RESPONSE OF BRAIN RESIDENT MICROGLIA TO KAINIC ACID-INDUCED HIPPOCAMPAL-LESIONS [J].
AKIYAMA, H ;
TOOYAMA, I ;
KONDO, H ;
IKEDA, K ;
KIMURA, H ;
MCGEER, EG ;
MCGEER, PL .
BRAIN RESEARCH, 1994, 635 (1-2) :257-268
[2]   Differential expression of thymosins β4 and β10 during rat cerebellum postnatal development [J].
Anadón, R ;
Moldes, IR ;
Carpintero, P ;
Evangelatos, G ;
Livianou, E ;
Leondiadis, L ;
Quintela, I ;
Cerviño, MC ;
Gómez-Márquez, J .
BRAIN RESEARCH, 2001, 894 (02) :255-265
[3]  
Bamburg J. R., 1991, NEURONAL CYTOSKELETO, P121
[4]   FISH E587 GLYCOPROTEIN, A MEMBER OF THE L1 FAMILY OF CELL-ADHESION MOLECULES, PARTICIPATES IN AXONAL FASCICULATION AND THE AGE-RELATED ORDER OF GANGLION-CELL AXONS IN THE GOLDFISH RETINA [J].
BASTMEYER, M ;
OTT, H ;
LEPPERT, CA ;
STUERMER, CAO .
JOURNAL OF CELL BIOLOGY, 1995, 130 (04) :969-976
[5]   ALTERATIONS IN ACTIN-BINDING BETA-THYMOSIN EXPRESSION ACCOMPANY NEURONAL DIFFERENTIATION AND MIGRATION IN RAT CEREBELLUM [J].
BORDER, BG ;
LIN, SC ;
GRIFFIN, WST ;
PARDUE, S ;
MORRISONBOGORAD, M .
JOURNAL OF NEUROCHEMISTRY, 1993, 61 (06) :2104-2114
[6]  
BRAY D, 1985, J NEUROSCI, V5, P3204
[7]   Neural cell recognition molecule L1:: from cell biology to human hereditary brain malformations [J].
Brümmendorf, T ;
Kenwrick, S ;
Rathjen, FG .
CURRENT OPINION IN NEUROBIOLOGY, 1998, 8 (01) :87-97
[8]   Expression of thymosin β4 messenger RNA in normal and kainate-treated rat forebrain [J].
Carpintero, P ;
Anadón, R ;
Díaz-Regueira, S ;
Gómez-Márquez, J .
NEUROSCIENCE, 1999, 90 (04) :1433-1444
[9]   THE THYMOSIN BETA(4) GENE IS STRONGLY ACTIVATED IN NEURAL TISSUES DURING EARLY POSTIMPLANTATION MOUSE DEVELOPMENT [J].
CARPINTERO, P ;
ANADON, R ;
DELAMO, FF ;
GOMEZMARQUEZ, J .
NEUROSCIENCE LETTERS, 1995, 184 (01) :63-66
[10]   Prion protein as trans-interacting partner for neurons is involved in neurite outgrowth and neuronal survival [J].
Chen, SZ ;
Mangé, A ;
Dong, L ;
Lehmann, S ;
Schachner, M .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2003, 22 (02) :227-233