title: DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy.
abstract: DJ-1 plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of Parkinson's disease. DJ-1 has a protease-like structure and transthyretin (TTR), a protein causing familial amyloidotic polyneuropathy (FAP), was identified as a substrate for DJ-1 protease in this study. Both TTR and DJ-1 were secreted into the culture medium under normal conditions, and secreted TTR was not aggregated. Under oxidative conditions, TTR but not DJ-1 was secreted into the culture medium, resulting in aggregation. Mirror images of both the expression patterns and solubility of DJ-1 and TTR were observed in tissues of FAP patients, and an unoxidized form of DJ-1, an inactive form, was secreted into the serum of FAP patients. These results suggest that oxidative stress to cells abrogates secretion of DJ-1 and that secreted DJ-1 degrades aggregated TTR to protect against the onset of FAP.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-8589, Japan.
authors.forename: Shizuyo
authors.initials: S
authors.lastname: Koide-Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niki
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Shingo
authors.initials: S
authors.lastname: Himeno
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taira
authors.forename: Sanae M M
authors.initials: SM
authors.lastname: Iguchi-Ariga
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000097:blood / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D008161:Lumbosacral Region / Q000473:pathology; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D041681:NIH 3T3 Cells; D009417:Nerve Tissue / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000378:metabolism* / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D010447:Peptide Hydrolases / Q000378:metabolism; D011228:Prealbumin / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D011499:Protein Processing, Post-Translational
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D015513:Oncogene Proteins; D011228:Prealbumin; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D010447:Peptide Hydrolases