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Molecular Species of Phospholipids with Very Long Chain Fatty Acids in Skin Fibroblasts of Zellweger Syndrome

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Lipids

Abstract

The ratio of C26:0/C22:0 fatty acids in patient lipids is widely accepted as a critical clinical criterion of peroxisomal diseases, such as Zellweger syndrome and X-linked adrenoleukodystrophy (X-ALD). However, phospholipid molecular species with very long chain fatty acids (VLCFA) have not been precisely characterized. In the present study, the structures of such molecules in fibroblasts of Zellweger syndrome and X-ALD were examined using LC–ESI–MS/MS analysis. In fibroblasts from Zellweger patients, a large number of VLCFA-containing molecular species were detected in several phospholipid classes as well as neutral lipids, including triacylglycerol and cholesteryl esters. Among these lipids, phosphatidylcholine showed the most diversity in the structures of VLCFA-containing molecular species. Some VLCFA possessed longer carbon chains and/or larger number of double bonds than C26:0-fatty acid (FA). Similar VLCFA were also found in other phospholipid classes, such as phosphatidylethanolamine and phosphatidylserine. In addition, VLCFA-containing phospholipid species showed some differences among fibroblasts from Zellweger patients. It appears that phospholipids with VLCFA, with or without double bonds, as well as C26:0-FA might affect cellular functions, thus leading to the pathogenesis of peroxisomal diseases, such as Zellweger syndrome and X-ALD.

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Abbreviations

ABCD1:

ATP-binding cassette protein D1

X-ALD:

X-linked adrenoleukodystrophy

CE:

Cholesteryl ester

LC–ESI–MS/MS:

Liquid chromatography–electrospray ionization–tandem mass spectrometry

MS:

Mass spectrometry

PtdCho or PC:

Phosphatidylcholine

PtdEtn or PE:

Phosphatidylethanolamine

PtdGro or PG:

Phosphatidylglycerol

PtdIns or PI:

Phosphatidylinositol

PtdSer or PS:

Phosphatidylserine

TAG or TG:

Triacylglycerol

VLCFA:

Very long chain fatty acid(s)

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Acknowledgments

This work was supported by a research grant for the study of Intractable Disease Project from the Ministry of Health, Labour and Welfare (T.I. N.S. and K.Y.), and a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan to K.H. (KAKENHI #24770114).

Author information

Author notes

  1. Kazutaka Ikeda

    Present address: Institute for Advanced Biosciences, Keio University, Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan

  2. Hiroki Nakanishi

    Present address: Research Center for Biosignal, Akita University, Akita, Akita, 010-8543, Japan

  3. Ryo Taguchi

    Present address: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi, 487-8501, Japan

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

    Kotaro Hama, Toru Nagai, Chiho Nishizawa, Noriko Satoh, Keizo Inoue & Kazuaki Yokoyama

  2. Department of Metabolome, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Kazutaka Ikeda, Hiroki Nakanishi & Ryo Taguchi

  3. Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Masashi Morita & Tsuneo Imanaka

  4. Division of Genomic Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Nobuyuki Shimozawa

  5. CREST, JST, Honcho, Kawaguchi, 332-0012, Saitama, Japan

    Ryo Taguchi & Kazuaki Yokoyama

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  1. Kotaro Hama
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Correspondence to Kazuaki Yokoyama.

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Hama, K., Nagai, T., Nishizawa, C. et al. Molecular Species of Phospholipids with Very Long Chain Fatty Acids in Skin Fibroblasts of Zellweger Syndrome. Lipids 48, 1253–1267 (2013). https://doi.org/10.1007/s11745-013-3848-5

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  • DOI: https://doi.org/10.1007/s11745-013-3848-5

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