Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann-Pick Disease Type C.

HAD–MS/MS LC–MS/MS N-acyl-phospholipids Niemann–Pick disease type C biomarkers chemical derivatization chemical diagnosis identification lysosphingomyelin-509 structural determination

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
10 Oct 2019
Historique:
received: 26 09 2019
revised: 06 10 2019
accepted: 08 10 2019
entrez: 30 10 2019
pubmed: 30 10 2019
medline: 1 4 2020
Statut: epublish

Résumé

Niemann-Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation-tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as

Identifiants

pubmed: 31658747
pii: ijms20205018
doi: 10.3390/ijms20205018
pmc: PMC6829288
pii:
doi:

Substances chimiques

Biomarkers 0
Lipids 0
Phosphorylcholine 107-73-3
Serine 452VLY9402

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Japan Society for the Promotion of Science
ID : 18K15699

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Auteurs

Masamitsu Maekawa (M)

Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. m-maekawa@tohoku.ac.jp.

Isamu Jinnoh (I)

Laboratory of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi 980-8574, Japan. i.jin.1994.s@gmail.com.

Yotaro Matsumoto (Y)

Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. yotaro.matsumoto.a5@tohoku.ac.jp.
Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aoba-Ku, Sendai, Miyagi 980-8578, Japan. yotaro.matsumoto.a5@tohoku.ac.jp.

Aya Narita (A)

Division of Child Neurology, Tottori University Hospital, 86 Nishi-machi, Yonago, Tottori 683-8503, Japan. aya.luce@nifty.com.

Ryuichi Mashima (R)

Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. mashima-r@ncchd.go.jp.

Hidenori Takahashi (H)

Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho Nakagyo-ku, Kyoto 604-8511, Japan. th1128ca@shimadzu.co.jp.

Anna Iwahori (A)

Laboratory of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi 980-8574, Japan. anna.iwahori.t8@dc.tohoku.ac.jp.

Daisuke Saigusa (D)

Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. saigusa@tohoku.ac.jp.
Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. saigusa@tohoku.ac.jp.

Kumiko Fujii (K)

Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. fujii@dokkyomed.ac.jp.

Ai Abe (A)

Laboratory of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi 980-8574, Japan. ai.abe.q2@dc.tohoku.ac.jp.

Katsumi Higaki (K)

Division of Functional Genomics, Research Centre for Bioscience and Technology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan. kh4060@med.tottori-u.ac.jp.

Shosei Yamauchi (S)

Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho Nakagyo-ku, Kyoto 604-8511, Japan. shosei-y@shimadzu.co.jp.

Yuji Ozeki (Y)

Department of Psychiatry, Shiga University of Medical Science, Setatsukiwacho, Otsu, Shiga 520-2192 Japan. ozeki@belle.shiga-med.ac.jp.

Kazutaka Shimoda (K)

Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. shimoda@dokkyomed.ac.jp.

Yoshihisa Tomioka (Y)

Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. yoshihisa.tomioka.a6@tohoku.ac.jp.
Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aoba-Ku, Sendai, Miyagi 980-8578, Japan. yoshihisa.tomioka.a6@tohoku.ac.jp.

Torayuki Okuyama (T)

Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. okuyama-t@ncchd.go.jp.

Yoshikatsu Eto (Y)

Advanced Clinical Research Center, Institute for Neurological Disorders, Furusawa-Miyako 255, Asou-ku, Kawasaki, Kanagawa 215-0026, Japan. yosh@sepia.ocn.ne.jp.

Kousaku Ohno (K)

Division of Child Neurology, Tottori University Hospital, 86 Nishi-machi, Yonago, Tottori 683-8503, Japan. ohno@sanmedia.or.jp.

Peter T Clayton (P)

Inborn Errors of Metabolism, Clinical and Molecular Genetics Unit, UCL Great Ormond Street Institute of Child Health. 30 Guilford Street, University College London, WC1N 1EH London, UK. peter.clayton@ucl.ac.uk.

Hiroaki Yamaguchi (H)

Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. hiroaki.yamaguchi@med.id.yamagata-u.ac.jp.
Laboratory of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi 980-8574, Japan. hiroaki.yamaguchi@med.id.yamagata-u.ac.jp.

Nariyasu Mano (N)

Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. mano@hosp.tohoku.ac.jp.
Laboratory of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi 980-8574, Japan. mano@hosp.tohoku.ac.jp.

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