Next Article in Journal
Caenorhabditis Elegans and Probiotics Interactions from a Prolongevity Perspective
Previous Article in Journal
Directed Evolution of an Improved Rubisco; In Vitro Analyses to Decipher Fact from Fiction
Previous Article in Special Issue
Current Challenges in Understanding the Cellular and Molecular Mechanisms in Niemann–Pick Disease Type C1
Open AccessArticle

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

1
Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
2
Laboratory of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi 980-8574, Japan
3
Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aoba-Ku, Sendai, Miyagi 980-8578, Japan
4
Division of Child Neurology, Tottori University Hospital, 86 Nishi-machi, Yonago, Tottori 683-8503, Japan
5
Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan
6
Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho Nakagyo-ku, Kyoto 604-8511, Japan
7
Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
8
Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan
9
Division of Functional Genomics, Research Centre for Bioscience and Technology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan
10
Department of Psychiatry, Shiga University of Medical Science, Setatsukiwacho, Otsu, Shiga 520-2192 Japan
11
Advanced Clinical Research Center, Institute for Neurological Disorders, Furusawa-Miyako 255, Asou-ku, Kawasaki, Kanagawa 215-0026, Japan
12
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
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 5018; https://doi.org/10.3390/ijms20205018
Received: 26 September 2019 / Revised: 6 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
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 N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509. View Full-Text
Keywords: Niemann–Pick disease type C; biomarkers; chemical diagnosis; lysosphingomyelin-509; N-acyl-phospholipids; LC–MS/MS; HAD–MS/MS; chemical derivatization; identification; structural determination Niemann–Pick disease type C; biomarkers; chemical diagnosis; lysosphingomyelin-509; N-acyl-phospholipids; LC–MS/MS; HAD–MS/MS; chemical derivatization; identification; structural determination
Show Figures

Graphical abstract

MDPI and ACS Style

Maekawa, M.; Jinnoh, I.; Matsumoto, Y.; Narita, A.; Mashima, R.; Takahashi, H.; Iwahori, A.; Saigusa, D.; Fujii, K.; Abe, A.; Higaki, K.; Yamauchi, S.; Ozeki, Y.; Shimoda, K.; Tomioka, Y.; Okuyama, T.; Eto, Y.; Ohno, K.; T Clayton, P.; Yamaguchi, H.; Mano, N. Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann–Pick Disease Type C. Int. J. Mol. Sci. 2019, 20, 5018.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop