Sympathetic neurons synthesize and secrete pro-nerve growth factor protein

被引:53
作者
Hasan, W
Pedchenko, T
Krizsan-Agbas, D
Baum, L
Smith, PG
机构
[1] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA
[2] Univ Kansas, Med Ctr, RL Smith Mental Retardat Res Ctr, Kansas City, KS 66160 USA
来源
JOURNAL OF NEUROBIOLOGY | 2003年 / 57卷 / 01期
关键词
sympathetic neurons; nerve growth factor; neuronal survival; autocrine growth factor; development;
D O I
10.1002/neu.10250
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Postmitotic sympathetic neuronal survival is dependent upon nerve growth factor (NGF) provided by peripheral targets, and this dependency serves as a central tenet of the neurotrophic hypothesis. In some other systems, NGF has been shown to play an autocrine role, although the pervasiveness and significance of this phenomenon within the nervous system remain unclear. We show here that rat sympathetic neurons synthesize and secrete NGF. NGF mRNA is expressed in nearly half of superior cervical ganglion sympathetic neurons at embryonic day 17, rising to over 90% in the early postnatal period, and declining in the adult. Neuronal immunoreactivity is reduced when retrograde transport is interrupted by axotomy, but persists in a subpopulation of neurons despite diminished mRNA expression, suggesting that intrinsic protein synthesis occurs. Cultured neonatal neurons express NGF mRNA, which is maintained even when they are undergoing apoptosis. To determine which NGF isoforms are secreted, we performed metabolic labeling and immunoprecipitation of NGF-immunoreactive proteins synthesized by cultured NGF-dependent and -independent neurons. Conditioned medium contained high molecular weight NGF precursor proteins, which varied depending upon the state of NGF dependence. Mature NGF was undetectable by these methods. High molecular weight NGF isoforms were also detected in ganglion homogenates, and persisted at diminished levels following axotomy. We conclude that sympathetic neurons express NGF mRNA, and synthesize and secrete pro-NGF protein. These findings suggest that a potential NGF-sympathetic neuron autocrine loop may exist in this prototypic target-dependent system, but that the secreted forms of this neurotrophin apparently do not support neuronal survival. (C) 2003 Wiley Periodicals, Inc.
引用
收藏
页码:38 / 53
页数:16
相关论文
共 82 条
[21]   The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease [J].
Fahnestock, M ;
Michalski, B ;
Xu, B ;
Coughlin, MD .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2001, 18 (02) :210-220
[22]   Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV [J].
Garaci, E ;
Caroleo, MC ;
Aloe, L ;
Aquaro, S ;
Piacentini, M ;
Costa, N ;
Amendola, A ;
Micera, A ;
Caliò, R ;
Perno, CF ;
Levi-Montalcini, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :14013-14018
[23]   Mapping the domains of the interaction of the vitamin D receptor and steroid receptor coactivator-1 [J].
Gill, RK ;
Atkins, LM ;
Hollis, BW ;
Bell, NH .
MOLECULAR ENDOCRINOLOGY, 1998, 12 (01) :57-65
[24]   Coordinate expression of NGF and α-smooth muscle actin mRNA and protein in cutaneous wound tissue of developing and adult rats [J].
Hasan, W ;
Zhang, RJ ;
Liu, MX ;
Warn, JD ;
Smith, PG .
CELL AND TISSUE RESEARCH, 2000, 300 (01) :97-109
[25]   Nerve growth factor expression in parasympathetic neurons: regulation by sympathetic innervation [J].
Hasan, W ;
Smith, PG .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (12) :4391-4397
[26]  
Hawrot E, 1979, Methods Enzymol, V58, P574
[27]   HIGH-AFFINITY NGF BINDING REQUIRES COEXPRESSION OF THE TRK PROTOONCOGENE AND THE LOW-AFFINITY NGF RECEPTOR [J].
HEMPSTEAD, BL ;
MARTINZANCA, D ;
KAPLAN, DR ;
PARADA, LF ;
CHAO, MV .
NATURE, 1991, 350 (6320) :678-683
[28]   RETROGRADE AXONAL-TRANSPORT OF NERVE GROWTH-FACTOR [J].
HENDRY, IA ;
STOCKEL, K ;
THOENEN, H ;
IVERSEN, LL .
BRAIN RESEARCH, 1974, 68 (01) :103-121
[29]   CHANGES OF NERVE GROWTH-FACTOR SYNTHESIS IN NONNEURONAL CELLS IN RESPONSE TO SCIATIC-NERVE TRANSECTION [J].
HEUMANN, R ;
KORSCHING, S ;
BANDTLOW, C ;
THOENEN, H .
JOURNAL OF CELL BIOLOGY, 1987, 104 (06) :1623-1631
[30]   RELATIONSHIP BETWEEN LEVELS OF NERVE GROWTH-FACTOR (NGF) AND ITS MESSENGER-RNA IN SYMPATHETIC-GANGLIA AND PERIPHERAL TARGET TISSUES [J].
HEUMANN, R ;
KORSCHING, S ;
SCOTT, J ;
THOENEN, H .
EMBO JOURNAL, 1984, 3 (13) :3183-3189