Mawaddah Ar Rochmah1,2, Yogik Onky Silvana Wijaya1, Nur Imma Fatimah Harahap1,3, Chisato Tode4, Atsuko Takeuchi4, Kazuki Ohuchi5, Masamitsu Shimazawa5, Hideaki Hara5, Michinori Funato6, Toshio Saito7, Kayoko Saito8, Poh San Lai9, Hiroyuki Awano10, Masakazu Shinohara1, Hisahide Nishio1,11, Emma Tabe Eko Niba1. 1. Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan. 2. Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia. 3. Department of Clinical Pathology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia. 4. Instrumental Analysis Center, Kobe Pharmaceutical University, Kobe, Japan. 5. Department of Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan. 6. Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan. 7. Division of Child Neurology, Department of Neurology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan. 8. Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan. 9. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 10. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. 11. Faculty of Medical Rehabilitation, Kobe Gakuin University, Kobe, Japan.
Abstract
BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration or loss of lower motor neurons. The survival of motor neuron (SMN) 1 gene, which produces the SMN protein, has been identified as a responsible gene for the disease. SMN is ubiquitously expressed in any tissue and may play an important role on the metabolism in the human body. However, no appropriate biomarkers reflecting the alteration in the metabolism in SMA have been identified. METHODS: Low-molecular-weight metabolites were extracted from plasma of 20 human infants (9 SMA type 1 patients and 11 controls) and 9 infant mice (5 SMA-model mice, 4 control mice), and derivatized with N-methyl-N-trimethylsilyltrifluoroacetamide. Finally, the derivatized products were applied to Gas Chromatography/Mass Spectrometry apparatus. To confirm the metabolite abnormality in SMA type 1 patients, we performed SMN-silencing experiment using a hepatocyte-derived cell line (HepG2). RESULTS: We performed a comprehensive metabolomics analysis of plasma from the patients with SMA type 1 and controls, and found that phosphoethanolamine (PEA) was significantly higher in the patients than in the controls. HepG2 experiment also showed that SMN-silencing increased PEA levels. However, comprehensive metabolomics analysis of plasma from SMA-model mice and control mice showed different profile compared to human plasma; there was no increase of PEA even in the SMA-model mice plasma. CONCLUSION: Our data suggested that PEA was one of the possible biomarkers of human SMA reflecting metabolic abnormalities due to the SMN protein deficiency.
BACKGROUND:Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration or loss of lower motor neurons. The survival of motor neuron (SMN) 1 gene, which produces the SMN protein, has been identified as a responsible gene for the disease. SMN is ubiquitously expressed in any tissue and may play an important role on the metabolism in the human body. However, no appropriate biomarkers reflecting the alteration in the metabolism in SMA have been identified. METHODS: Low-molecular-weight metabolites were extracted from plasma of 20 humaninfants (9 SMA type 1 patients and 11 controls) and 9 infant mice (5 SMA-model mice, 4 control mice), and derivatized with N-methyl-N-trimethylsilyltrifluoroacetamide. Finally, the derivatized products were applied to Gas Chromatography/Mass Spectrometry apparatus. To confirm the metabolite abnormality in SMA type 1 patients, we performed SMN-silencing experiment using a hepatocyte-derived cell line (HepG2). RESULTS: We performed a comprehensive metabolomics analysis of plasma from the patients with SMA type 1 and controls, and found that phosphoethanolamine (PEA) was significantly higher in the patients than in the controls. HepG2 experiment also showed that SMN-silencing increased PEA levels. However, comprehensive metabolomics analysis of plasma from SMA-model mice and control mice showed different profile compared to human plasma; there was no increase of PEA even in the SMA-model mice plasma. CONCLUSION: Our data suggested that PEA was one of the possible biomarkers of human SMA reflecting metabolic abnormalities due to the SMN protein deficiency.
Authors: P E McAndrew; D W Parsons; L R Simard; C Rochette; P N Ray; J R Mendell; T W Prior; A H Burghes Journal: Am J Hum Genet Date: 1997-06 Impact factor: 11.025
Authors: S Lefebvre; L Bürglen; S Reboullet; O Clermont; P Burlet; L Viollet; B Benichou; C Cruaud; P Millasseau; M Zeviani Journal: Cell Date: 1995-01-13 Impact factor: 41.582
Authors: Richard S Finkel; Thomas O Crawford; Kathryn J Swoboda; Petra Kaufmann; Peter Juhasz; Xiaohong Li; Yu Guo; Rebecca H Li; Felicia Trachtenberg; Suzanne J Forrest; Dione T Kobayashi; Karen S Chen; Cynthia L Joyce; Thomas Plasterer Journal: PLoS One Date: 2012-04-27 Impact factor: 3.240