Sialic acid deficiency is associated with oxidative stress leading to muscle atrophy and weakness in GNE myopathy

Human Molecular Genetics
Anna ChoSatoru Noguchi

Abstract

Sialic acids are monosaccharides found in terminal sugar chains of cell surfaces and proteins; they have various biological functions and have been implicated in health and disease. Genetic defects of the GNE gene which encodes a critical bifunctional enzyme for sialic acid biosynthesis, lead to GNE myopathy, a disease manifesting with progressive muscle atrophy and weakness. The likely mechanism of disease is a lack of sialic acids. There remains, however, an unexplained link between hyposialylation and the muscle atrophy and weakness. In this study, we found that muscle proteins were highly modified by S-nitrosylation, and that oxidative stress-responsive genes were significantly upregulated, in hyposialylated muscles from human GNE myopathy patients and model mice. In both in vitro and in vivo models, the production of reactive oxygen species (ROS) was elevated with cellular hyposialylation, and increasing overall sialylation by extrinsic sialic acid intake reduced ROS and protein S-nitrosylation. More importantly, the antioxidant, oral N-acetylcysteine led to amelioration of the muscle atrophy and weakness in Gne mutant mice. Our data provide evidence of additional important function of sialic acids as a ROS scavenger in sk...Continue Reading

References

Jul 1, 1981·Journal of the Neurological Sciences·I NonakaE Satoyoshi
Mar 31, 1995·Clinica Chimica Acta; International Journal of Clinical Chemistry·G J van KampE C Wolters
Dec 1, 1994·The Journal of Clinical Investigation·M B ReidA A Leis
Mar 1, 1993·Free Radical Biology & Medicine·M Sato, I Bremner
May 21, 1999·Science·O T KepplerM Pawlita
Jul 3, 1999·The Journal of Biological Chemistry·Y J Lee, E Shacter
Sep 18, 1999·Free Radical Biology & Medicine·H Wang, J A Joseph
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·M D GomesA L Goldberg
Mar 5, 2003·Cellular and Molecular Life Sciences : CMLS·M ZafarullahM Ahmad
Oct 22, 2003·Clinica Chimica Acta; International Journal of Clinical Chemistry·Kalyan GoswamiSanat Kumar Sen
Jun 25, 2004·Metabolic Brain Disease·Susan J van RensburgNico de Villiers
Jan 29, 2005·Current Neurology and Neuroscience Reports·Ikuya NonakaIchizo Nishino
Oct 18, 2005·Muscle & Nerve·Susan C Kandarian, Robert W Jackman
Feb 21, 2006·Antioxidants & Redox Signaling·Roberta KiffinAna Maria Cuervo
Jun 17, 2006·The Journal of Physiology·Marie E SandströmAbram Katz
Nov 11, 2006·Journal of Applied Physiology·James G Tidball, Michelle Wehling-Henricks
Feb 3, 2007·Muscle & Nerve·Jennifer S Moylan, Michael B Reid
May 9, 2007·FEBS Letters·Yuki OgasawaraKazuyuki Ishii
Dec 7, 2007·Cell Metabolism·Cristina MammucariMarco Sandri
Sep 4, 2009·Trends in Molecular Medicine·Matthew W FosterJonathan S Stamler
Jul 6, 2010·TheScientificWorldJournal·Tiziana ParasassiFulvio Ursini
Apr 5, 2011·Antioxidants & Redox Signaling·Scott K PowersDavid S Criswell
Nov 17, 2011·The Journal of Biological Chemistry·Jin Young BaekTong-Shin Chang
Jan 10, 2012·Annual Review of Immunology·Shiv PillaiHamid Mattoo
Jun 12, 2012·Oxidative Medicine and Cellular Longevity·Enrico DoriaFulvio Marzatico
Mar 19, 2013·International Journal of Molecular Sciences·Branislav Ruttkay-NedeckyRene Kizek
Apr 30, 2013·Handbook of Clinical Neurology·J Jaeken

❮ Previous
Next ❯

Citations

Oct 20, 2018·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Nuria CarrilloMarjan Huizing
Nov 21, 2019·Neurology India·Kapila AwasthiSudha Bhattacharya
Oct 9, 2019·Annual Review of Pathology·Marta Margeta
May 4, 2018·Orphanet Journal of Rare Diseases·Oksana PogoryelovaAndreas Roos
Oct 31, 2018·Frontiers in Neuroscience·Shreedarshanee DeviRanjana Arya
Jan 28, 2020·Journal of Neuromuscular Diseases·Hadar BenyaminiStella Mitrani-Rosenbaum
Aug 23, 2020·International Journal of Molecular Sciences·Alexander Mensch, Stephan Zierz
May 23, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yuxiao LiaoWei Yang
Jul 3, 2021·Cells·Nicola MoscaGiorgio Tasca
Jul 15, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Nuria CarrilloWilliam A Gahl
Sep 24, 2021·Journal of Cellular Biochemistry·Priyanka ChaudharyRanjana Arya
Nov 22, 2020·Neurology·Chia-Ying LiuNuria Carrillo

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.