title: ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis.
abstract: The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)(H46R) rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins-inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1(H46R) rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1(H46R) rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Hirotaka
authors: H
authors: Tanaka
authors: Masamitsu
authors: M
authors: Shimazawa
authors: Masafumi
authors: M
authors: Takata
authors: Hideo
authors: H
authors: Kaneko
authors: Kazuhiro
authors: K
authors: Tsuruma
authors: Tsunehiko
authors: T
authors: Ikeda
authors: Hitoshi
authors: H
authors: Warita
authors: Masashi
authors: M
authors: Aoki
authors: Mitsunori
authors: M
authors: Yamada
authors: Hitoshi
authors: H
authors: Takahashi
authors: Isao
authors: I
authors: Hozumi
authors: Hiroshi
authors: H
authors: Minatsu
authors: Takashi
authors: T
authors: Inuzuka
authors: Hideaki
authors: H
authors: Hara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood*; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053491:Proteinase Inhibitory Proteins, Secretory / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D006023:Glycoproteins; C091236:ITIH4 protein, human; C000599468:ITIH4 protein, rat; D053491:Proteinase Inhibitory Proteins, Secretory; C000606290:SOD1 protein, human; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1