HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 12, 11402-11407, March 19, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/12/11402    most recent M313171200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Noguchi, S. Articles by Nishino, I. Search for Related Content PubMed PubMed Citation Articles by Noguchi, S. Articles by Nishino, I. Social Bookmarking                      What's this?

Reduction of UDP-N-acetylglucosamine 2-Epimerase/N-Acetylmannosamine Kinase Activity and Sialylation in Distal Myopathy with Rimmed Vacuoles^*

Satoru Noguchi¶, Yoko Keira, Kumiko Murayama, Megumu Ogawa, Masako Fujita, Genri Kawahara, Yasushi Oya||, Masaoki Imazawa**, Yu-ichi Goto, Yukiko K. Hayashi, Ikuya Nonaka||, and Ichizo Nishino

From the Department of Neuromuscular Research, ^**Division of Radiation Protection, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, and ^||National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan

Distal myopathy with rimmed vacuoles is an autosomal recessive muscle disease with preferential involvement of the tibialis anterior that spares the quadriceps muscles in young adulthood. In a Japanese patient with distal myopathy with rimmed vacuoles, we identified pathogenic mutations in the gene encoding the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase, which catalyzes the initial two steps in the biosynthesis of sialic acid. In this study, we demonstrated the relationship between the genetic mutations and enzymatic activities using an in vitro expression assay system. Furthermore, we also showed that the levels of sialic acid in muscle and primary cultured cells from DMRV patients were reduced to 60–75% of control. The reactivities to lectins were also variable in some myofibers, suggesting that hyposialylation and abnormal glycosylation in muscles may contribute to the focal accumulations of autophagic vacuoles, amyloid deposits, or both in patient muscle tissue. The addition of ManNAc and NeuAc to primary cultured cells normalized sialylation levels, thus demonstrating the therapeutic potential of these compounds for this disease.

Received for publication, December 3, 2003 , and in revised form, December 30, 2003.

^* This study was supported by a grant for research on psychiatric and neurological diseases and mental health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 81-423412712; Fax: 81-423461742; E-mail: noguchi{at}ncnp.go.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Eisenberg, N. Novershtern, Z. Itzhaki, M. Becker-Cohen, M. Sadeh, P. H.G.M. Willems, N. Friedman, W. J.H. Koopman, and S. Mitrani-Rosenbaum Mitochondrial processes are impaired in hereditary inclusion body myopathy Hum. Mol. Genet., December 1, 2008; 17(23): 3663 - 3674. [Abstract] [Full Text] [PDF]

				M. C. V. Malicdan, S. Noguchi, Y. K. Hayashi, and I. Nishino Muscle weakness correlates with muscle atrophy and precedes the development of inclusion body or rimmed vacuoles in the mouse model of DMRV/hIBM Physiol Genomics, September 17, 2008; 35(1): 106 - 115. [Abstract] [Full Text] [PDF]

				M. C. V. Malicdan, S. Noguchi, I. Nonaka, Y. K. Hayashi, and I. Nishino A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy Hum. Mol. Genet., November 15, 2007; 16(22): 2669 - 2682. [Abstract] [Full Text] [PDF]

				M. C. V. Malicdan, S. Noguchi, I. Nonaka, Y. K. Hayashi, and I. Nishino A Gne knockout mouse expressing human V572L mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy Hum. Mol. Genet., January 15, 2007; 16(2): 115 - 128. [Abstract] [Full Text] [PDF]

				Z. Wang, Z. Sun, A. V. Li, and K. J. Yarema Roles for UDP-GlcNAc 2-Epimerase/ManNAc 6-Kinase outside of Sialic Acid Biosynthesis: MODULATION OF SIALYLTRANSFERASE AND BiP EXPRESSION, GM3 AND GD3 BIOSYNTHESIS, PROLIFERATION, AND APOPTOSIS, AND ERK1/2 PHOSPHORYLATION J. Biol. Chem., September 15, 2006; 281(37): 27016 - 27028. [Abstract] [Full Text] [PDF]

				E. Ricci, A. Broccolini, T. Gidaro, R. Morosetti, C. Gliubizzi, R. Frusciante, G. M. Di Lella, P. A. Tonali, and M. Mirabella NCAM is hyposialylated in hereditary inclusion body myopathy due to GNE mutations Neurology, March 14, 2006; 66(5): 755 - 758. [Abstract] [Full Text] [PDF]

				S. E. Sparks, C. Ciccone, M. Lalor, E. Orvisky, R. Klootwijk, P. J. Savelkoul, M. C. Dalakas, D. M. Krasnewich, W. A. Gahl, and M. Huizing Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities in human hereditary inclusion body myopathy Glycobiology, November 1, 2005; 15(11): 1102 - 1110. [Abstract] [Full Text] [PDF]

				L-S Ro, G-J Lee-Chen, Y-R Wu, M Lee, P-Y Hsu, and C-M Chen Phenotypic variability in a Chinese family with rimmed vacuolar distal myopathy J. Neurol. Neurosurg. Psychiatry, May 1, 2005; 76(5): 752 - 755. [Abstract] [Full Text] [PDF]

				Y. Tajima, E. Uyama, S. Go, C. Sato, N. Tao, M. Kotani, H. Hino, A. Suzuki, Y. Sanai, K. Kitajima, et al. Distal Myopathy with Rimmed Vacuoles: Impaired O-Glycan Formation in Muscular Glycoproteins Am. J. Pathol., April 1, 2005; 166(4): 1121 - 1130. [Abstract] [Full Text] [PDF]