Glial cell line-derived neurotrophic factor up-regulates GTP-cyclohydrolase I activity and tetrahydrobiopterin levels in primary dopaminergic neurones

被引:22
作者
Bauer, M
Suppmann, S
Meyer, M
Hesslinger, C
Gasser, T
Widmer, HR
Ueffing, M
机构
[1] LMU Munchen, Klinikum Grosshadern, Dept Neurol, Munich, Germany
[2] GSF Munich, Natl Res Ctr Environm & Hlth, Inst Human Genet, Munich, Germany
[3] LMU Munchen, Klinikum Innenstadt, Clin Cooperat Grp Ophthalmogenet, Munich, Germany
[4] Univ So Denmark, Odense Univ, Dept Anat & Neurobiol, Odense C, Denmark
[5] Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, Frankfurt, Germany
[6] Univ Bern, Inselspital, Dept Neurosurg, CH-3010 Bern, Switzerland
关键词
dopaminergic neurones; glial cell line-derived neurotrophic factor; GTP-cyclohydrolase I; ventral mesencephalon;
D O I
10.1046/j.1471-4159.2002.01074.x
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
Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurones against toxic and physical damage. In addition, GDNF promotes differentiation and structural integrity of dopaminergic neurones. Here we show that GDNF can support the function of primary dopaminergic neurones by triggering activation of GTP-cyclohydrolase I (GTPCH I), a key enzyme in catecholamine biosynthesis. GDNF stimulation of primary dopaminergic neurones expressing both tyrosine 3-monooxygenase and GTPCH I resulted in a dose-dependent doubling of GTPCH I activity, and a concomitant increase in tetrahydrobiopterin levels whereas tyrosine 3-monooxygenase activity was not altered. Actinomycin D, asan inhibitor of de novo biosynthesis, abolished any GDNF-mediated up-regulation of GTPCH I activity. However, GTPCH I mRNA levels in primary dopaminergic neurones were not altered by GDNF treatment, suggesting that the mode of action for that up-regulation is not directly connected to the regulation of GTPCH I transcription. We conclude that GDNF, in addition to its action in structural differentiation, also promotes differentiation regarding expression and enzymatic activity of a crucial component in the dopaminergic biosynthetic pathway.
引用
收藏
页码:1300 / 1310
页数:11
相关论文
共 54 条
  • [1] ESTIMATION OF NUCLEAR POPULATION FROM MICROTOME SECTIONS
    ABERCROMBIE, M
    [J]. ANATOMICAL RECORD, 1946, 94 (02): : 239 - 247
  • [2] REGULATION OF GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE AND TETRAHYDROBIOPTERIN LEVELS AND THE ROLE OF THE COFACTOR IN TYROSINE HYDROXYLATION IN PRIMARY CULTURES OF ADRENOMEDULLARY CHROMAFFIN CELLS
    ABOUDONIA, MM
    WILSON, SP
    ZIMMERMAN, TP
    NICHOL, CA
    VIVEROS, OH
    [J]. JOURNAL OF NEUROCHEMISTRY, 1986, 46 (04) : 1190 - 1199
  • [3] Differential effects of glial cell line-derived neurotrophic factor and neurturin on developing and adult substantia nigra dopaminergic neurons
    Åkerud, P
    Alberch, J
    Eketjäll, S
    Wagner, J
    Arenas, E
    [J]. JOURNAL OF NEUROCHEMISTRY, 1999, 73 (01) : 70 - 78
  • [4] Anastasiadis PZ, 1996, MOL PHARMACOL, V49, P149
  • [5] Tetrahydrobiopterin enhances apoptotic PC12 cell death following withdrawal of trophic support
    Anastasiadis, PZ
    Jiang, H
    Bezin, L
    Kuhn, DM
    Levine, RA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (12) : 9050 - 9058
  • [6] Nonviral glial cell-derived neurotrophic factor gene transfer enhances survival of cultured dopaminergic neurons and improves their function after transplantation in a rat model of Parkinson's disease
    Bauer, M
    Meyer, M
    Grimm, L
    Meitinger, T
    Zimmer, J
    Gasser, T
    Ueffing, M
    Widmer, HR
    [J]. HUMAN GENE THERAPY, 2000, 11 (11) : 1529 - 1541
  • [7] GDNF induces a dystonia-like state in neonatal rats and stimulates dopamine and serotonin synthesis
    Beck, KD
    Irwin, I
    Valverde, J
    Brennan, TJ
    Langston, JW
    Hefti, F
    [J]. NEURON, 1996, 16 (03) : 665 - 673
  • [8] MESENCEPHALIC DOPAMINERGIC-NEURONS PROTECTED BY GDNF FROM AXOTOMY-INDUCED DEGENERATION IN THE ADULT BRAIN
    BECK, KD
    VALVERDE, J
    ALEXI, T
    POULSEN, K
    MOFFAT, B
    VANDLEN, RA
    ROSENTHAL, A
    HEFTI, F
    [J]. NATURE, 1995, 373 (6512) : 339 - 341
  • [9] A TYROSINE-HYDROXYLASE ASSAY IN MICROWELLS USING COUPLED NONENZYMATIC DECARBOXYLATION OF DOPA
    BOSTWICK, JR
    LE, WD
    [J]. ANALYTICAL BIOCHEMISTRY, 1991, 192 (01) : 125 - 130
  • [10] GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR SUPPORTS SURVIVAL OF INJURED MIDBRAIN DOPAMINERGIC-NEURONS
    BOWENKAMP, KE
    HOFFMAN, AF
    GERHARDT, GA
    HENRY, MA
    BIDDLE, PT
    HOFFER, BJ
    GRANHOLM, ACE
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 355 (04) : 479 - 489