Protective effect of planarian DJ-1 against 6-hydroxydopamine-induced neurotoxicity

• Published in: Neuroscience research 2012-12, Vol.74 (3-4), p.277-283
• Main Authors: Tsushima, Jun, Nishimura, Kaneyasu, Tashiro, Natsuka, Takata, Kazuyuki, Ashihara, Eishi, Yoshimoto, Kanji, Ariga, Hiroyoshi, Agata, Kiyokazu, Kitamura, Yoshihisa
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; 6-Hydroxydopamine-induced neurotoxicity; Adrenergic Agents - toxicity; Amino Acid Sequence; Animals; Antioxidants; Blotting, Western; Cell death; Cell Line, Tumor; Central nervous system; Chaperones; DJ-1; Dopamine; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dugesia japonica; Fluorescent Antibody Technique; Humans; Hybridization analysis; In Situ Hybridization; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Molecular Sequence Data; Movement disorders; mRNA; Mutation; Nervous system; Neuroblastoma; Neurodegenerative diseases; Neuroprotection; Neurotoxicity; Neurotoxins; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Oncogenes; Oxidative stress; Oxidopamine - toxicity; PARK7 protein; Parkinson's disease; Pharynx; Planarians; Planarians - genetics; Planarians - metabolism; Protein Deglycase DJ-1; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2012.09.003

► We isolated planarian DJ-1, causative gene of familial Parkinson's disease, PARK7. ► Planarian DJ-1 protein conserved cystein residue and leucine residue. ► DjDJ-1 mRNA was expressed throughout the body, such as the CNS, cells and stem cells. ► Planarian DJ-1 conserved the functions as antioxidant and neuroprotection. DJ-1/PARK7 has multiple functions as an antioxidant, an oncogene, and a molecular chaperone in vertebrates, and loss-of-function mutations in DJ-1 cause early onset of Parkinson's disease. However, the function of invertebrate DJ-1 remains unknown. In order to investigate the function of planarian DJ-1, we isolated the planarian DJ-1 gene Dugesia japonica DJ-1 (DjDJ-1) and analyzed its expression and function. In situ hybridization analysis revealed that DjDJ-1 mRNA was expressed throughout the body, including the central nervous system, cells surrounding the pharynx, and stem cells. Planarian DjDJ-1 protein exhibited antioxidant function, similar to human DJ-1, as evidenced by the fact that recombinant DjDJ-1 protein reduced reactive oxygen species and protected human neuroblastoma SH-SY5Y cells from cell death. In addition, dopaminergic neurons in DjDJ-1(RNAi) planarians became susceptible to 6-hydroxydopamine, a dopaminergic neurotoxin. These results suggest that planarians have a DJ-1 ortholog, which has conserved antioxidant and neuroprotective functions.