GDNF modulates HO-1 expression in substantia nigra postnatal cell cultures

• Author(s): Saavedra, Ana ; Baltazar, Graça ; Carvalho, Caetana M. ; Duarte, Emília P.
• Date: 2005
• Persistent ID: http://hdl.handle.net/10316/5358
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): Astrocytes; Dopaminergic neurons; Glial cell line-derived neurotrophic factor; Heme oxygenase-1; Oxidative stress; Parkinson disease; Free radicals
• Document Type: Article
• Language: English

Description

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. http://www.sciencedirect.com/science/article/B6T38-4GY83GS-1/1/db5c1961511769a30a115fcbfcd902cf