Transcriptional activation of the human brain-derived neurotrophic factor gene promoter III by dopamine signaling in NT2/N neurons.
We have identified a functional cAMP-response element (CRE) in the human brain-derived neurotrophic factor (BDNF) gene promoter III and established that it participated in the modulation of BDNF expression in NT2/N neurons via downstream signaling from the D1 class of dopamine (DA) receptors. The up-regulation of BDNF expression, in turn, produced neuroprotective signals through receptor tyrosine kinase B (TrkB) and promoted cell survival under the conditions of oxygen and glucose deprivation. To our knowledge this is the first evidence showing the presence of a functional CRE in the human BDNF gene and the role of DA signaling in establishing transcriptional competence of CRE in post-mitotic NT2/N neurons. This ability of DA to regulate the expression of the BDNF survival factor has a profound significance for the nigrostriatal pathway, because it indicates the existence of a feedback loop between the neutrophin, which promotes both the maturation and survival of dopaminergic neurons, and the neurotransmitter, which the mature neurons ultimately produce and release.
Neurobiology Program, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada. hung.fang@nrc.ca
Hung
H
Fang
Joanne
J
Chartier
Caroline
C
Sodja
Angele
A
Desbois
Maria
M
Ribecco-Lutkiewicz
P Roy
PR
Walker
Marianna
M
Sikorska
D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D020813:Receptor, trkB / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D017447:Receptors, Dopamine D1; D003994:Bucladesine; D004247:DNA; D000242:Cyclic AMP; D020813:Receptor, trkB; D004298:Dopamine