GDNF modulates HO-1 expression in substantia nigra postnatal cell cultures |
| |
Authors: | Saavedra Ana Baltazar Graça Carvalho Caetana M Duarte Emília P |
| |
Institution: | aCenter for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal bDepartment of Health Sciences, University of Beira Interior, 6201-001 Covilhã, Portugal cDepartment of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal |
| |
Abstract: | Heme oxygenase-1 (HO-1) has been strongly highlighted because of its induction in many cell types by toxic stimuli, including oxidative stress. The intense HO-1 immunostaining in the substantia nigra of Parkinson disease (PD) patients suggests its involvement in the pathogenesis of this neurodegenerative disease. In this work we investigated HO-1 expression in rat substantia nigra postnatal cell cultures under conditions mimicking dopamine toxicity and its modulation by glial cell line-derived neurotrophic factor (GDNF), a potent neuroprotective factor for dopaminergic neurons. In neuron–glia cultures, we found that H2O2, a product of dopamine metabolism, or l-3,4-dihydroxyphenylalanine (l-DOPA), the dopamine precursor used in the therapy of PD, induced a fast up-regulation of HO-1 mRNA and protein levels, followed by a secondary down-regulation. H2O2 and l-DOPA also increased HO-1 expression in astrocyte cultures, but with a delayed time course in H2O2-treated cultures. HO-1 expression was decreased in neuron–glia cultures under conditions under which GDNF up-regulation was observed. Because exogenously applied GDNF prevented HO-1 up-regulation in cultures treated with H2O2 or l-DOPA, and antibody neutralization of GDNF prevented the secondary HO-1 down-regulation observed in neuron–glia cultures, we propose that GDNF negatively modulates HO-1 expression induced by oxidative stress. To our knowledge, this is the first report showing the modulation of HO-1 expression by GDNF. |
| |
Keywords: | Astrocytes Dopaminergic neurons Glial cell line-derived neurotrophic factor Heme oxygenase-1 Oxidative stress Parkinson disease Free radicals |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|