GDNF modulates HO-1 expression in substantia nigra postnatal cell cultures |
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| Institution: | 1. Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal;2. Department of Health Sciences, University of Beira Interior, 6201-001 Covilhã, Portugal;3. Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal;1. Accenture, Philippines;2. School of Management, University of Asia and the Pacific, Metro Manila, Philippines;1. School of Mechanical and Aerospace Engineering, Jilin University, Changchun, 130022, China;2. Weihai Institute for Bionics-Jilin University, Weihai, 264200, China;1. State Key Laboratory for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, National Engineering Laboratory for Green Chemical Productions of Alcohols-Ethers-Esters, and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China;2. Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164, USA;1. Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China;2. Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, No. 1 Wenhai Road, Qingdao, 266237, China;3. University of Chinese Academy of Sciences, Beijing, 100049, China |
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| 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. |
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