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ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis |
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| Authors: | Hirotaka Tanaka Masamitsu Shimazawa Masafumi Takata Hideo Kaneko Kazuhiro Tsuruma Tsunehiko Ikeda Hitoshi Warita Masashi Aoki Mitsunori Yamada Hitoshi Takahashi Isao Hozumi Hiroshi Minatsu Takashi Inuzuka Hideaki Hara |
| Affiliation: | 1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan 2. Department of Clinical Research, National Hospital Organization Nagara Medical Center, 1300-7 Nagara, Gifu, 502-8558, Japan 3. Department of Pediatrics, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan 4. Department of Ophthalmology, Osaka Medical College, 2-7 Diagaku-machi, Takatsuki, 569-8686, Japan 5. Department of Neurology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan 6. Department of Clinical Research, National Hospital Organization, Saigata National Hospital, 468-1, Saigata, Oogata-ku, Niigata, 949-3193, Japan 7. Department of Pathology, Brain Research Institute, Niigata University, 1-757, Asahimachi-dori, Chuo-ku, Niigata, 951-8585, Japan 8. Medical Therapeutics and Molecular Therapeutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan 9. Department of Pediatric Surgery, National Hospital Organization Nagara Medical Center, 1300-7 Nagara, Gifu, 502-8558, Japan 10. Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan |
| 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 SOD1H46R 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 SOD1H46R 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. |
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