Cutaneous dyspigmentation in patients with ganglioside GM3 synthase deficiency

2013 ◽  
Vol 161 (4) ◽  
pp. 875-879 ◽  
Author(s):  
Heng Wang ◽  
Alicia Bright ◽  
Baozhong Xin ◽  
J.R. Bockoven ◽  
Amy S. Paller
Keyword(s):  
Ganglioside Gm3 ◽  
Gm3 Synthase

scholarly journals Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti

2009 ◽  
Vol 106 (23) ◽  
pp. 9483-9488 ◽  
Author(s):  
M. Yoshikawa ◽  
S. Go ◽  
K. Takasaki ◽  
Y. Kakazu ◽  
M. Ohashi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Organ Of Corti ◽  
Ganglioside Gm3 ◽  
Gm3 Synthase

Assay Development and Screening for the Identification of Ganglioside GM3 Synthase Inhibitors

Biochemistry ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 1242-1251
Author(s):  
Kenji Yamanaka ◽  
Yu Takahashi ◽  
Yuya Azuma ◽  
Yoshiji Hantani
Keyword(s):  
Assay Development ◽  
Ganglioside Gm3 ◽  
Gm3 Synthase

scholarly journals ST3GAL5-Related Disorders: A Deficiency in Ganglioside Metabolism and a Genetic Cause of Intellectual Disability and Choreoathetosis

2018 ◽  
Vol 33 (13) ◽  
pp. 825-831 ◽  
Author(s):  
Eliza Gordon-Lipkin ◽  
Julie S. Cohen ◽  
Siddharth Srivastava ◽  
Bruno P. Soares ◽  
Eric Levey ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Neurodevelopmental Disorder ◽  
Failure To Thrive ◽  
Ganglioside Gm3 ◽  
Normal Birth ◽  
Pathogenic Variants ◽  
Gm3 Synthase ◽  
Whole Exome ◽  
Ganglioside Metabolism ◽  
Autosomal Recessive Condition

GM3 synthase deficiency is due to biallelic pathogenic variants in ST3GAL5, which encodes a sialyltransferase that synthesizes ganglioside GM3. Key features of this rare autosomal recessive condition include profound intellectual disability, failure to thrive and infantile onset epilepsy. We expand the phenotypic spectrum with 3 siblings who were found by whole exome sequencing to have a homozygous pathogenic variant in ST3GAL5, and we compare these cases to those previously described in the literature. The siblings had normal birth history, subsequent developmental stagnation, profound intellectual disability, choreoathetosis, failure to thrive, and visual and hearing impairment. Ichthyosis and self-injurious behavior are newly described in our patients and may influence clinical management. We conclude that GM3 synthase deficiency is a neurodevelopmental disorder with consistent features of profound intellectual disability, choreoathetosis, and deafness. Other phenotypic features have variable expressivity, including failure to thrive, epilepsy, regression, vision impairment, and skin findings. Our analysis demonstrates a broader phenotypic range of this potentially under-recognized disorder.

Ganglioside GM3 participates in the TGF-β1-induced epithelial–mesenchymal transition of human lens epithelial cells

2012 ◽  
Vol 449 (1) ◽  
pp. 241-251 ◽  
Author(s):  
Seok-Jo Kim ◽  
Tae-Wook Chung ◽  
Hee-Jung Choi ◽  
Choong-Hwan Kwak ◽  
Kwon-Ho Song ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Ganglioside Gm3 ◽  
Mesenchymal Transition ◽  
Human Lens Epithelial Cells ◽  
Gm3 Synthase ◽  
Tgf Β1

TGF-β (transforming growth factor-β)-induced EMT (epithelial–mesenchymal transition) induces the proliferation and migration of the HLE (human lens epithelial) cells. Ganglioside GM3, simple sialic-acid-containing glycosphingolipids on mammalian cell membranes, regulates various pathological phenomena such as insulin resistance and tumour progression. However, the relationship between ganglioside GM3 and TGF-β-induced EMT in the HLE B-3 cells is poorly understood. In the present study we demonstrated that ganglioside GM3 was involved in TGF-β1-induced EMT in HLE B-3 cells. Our results indicated that the expression of ganglioside GM3 and GM3 synthase mRNA were significantly increased in TGF-β1-induced HLE B-3 cells. Reporter gene analysis also demonstrated that transcriptional activation of the GM3 synthase gene was regulated by Sp1 (specificity protein 1) in HLE B-3 cells upon TGF-β1 stimulation. Interestingly, the inhibition of ganglioside GM3 expression by d-PDMP [d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol] and GM3 synthase shRNA (short hairpin RNA) resulted significantly in the suppression of cell migration and EMT-related signalling in HLE B-3 cells stimulated by TGF-β. Furthermore, exogenous treatment of ganglioside GM3 rescued the expression of EMT molecules and cell migration suppressed by the depletion of ganglioside GM3 in TGF-β1-induced HLE B-3 cells. We also found that ganglioside GM3 interacted with TGFβRs (TGF-β receptors) in TGF-β1-induced HLE B-3 cells. Taken together, these results suggest that ganglioside GM3 induced by TGF-β1 regulates EMT by potential interaction with TGFβRs.

scholarly journals Oral Ganglioside Supplement Improves Growth and Development in Patients with Ganglioside GM3 Synthase Deficiency

2018 ◽  
pp. 9-20 ◽  
Author(s):  
Heng Wang ◽  
Valerie Sency ◽  
Paul McJarrow ◽  
Alicia Bright ◽  
Qianyang Huang ◽  
...  
Keyword(s):  
Growth And Development ◽  
Ganglioside Gm3 ◽  
Gm3 Synthase

scholarly journals Enhanced Susceptibility to Chemoconvulsant-Induced Seizures in Ganglioside GM3 Synthase Knockout Mice

ASN NEURO ◽  
2020 ◽  
Vol 12 ◽  
pp. 175909142093817
Author(s):  
Fu-Lei Tang ◽  
Jing Wang ◽  
Yukata Itokazu ◽  
Robert K. Yu
Keyword(s):  
Intellectual Disability ◽  
Dentate Gyrus ◽  
Knockout Mice ◽  
Seizure Susceptibility ◽  
Hippocampal Dentate Gyrus ◽  
Ganglioside Gm3 ◽  
Gm3 Synthase ◽  
Intractable Seizures ◽  
Key Enzyme ◽  
Normal Controls

Ganglioside GM3 synthase (α-2,3-sialyltransferase, ST3GAL5, GM3S) is a key enzyme involved in the biosynthesis of gangliosides. ST3GAL5 deficiency causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest deafness, severe irritability, intractable seizures, and profound intellectual disability. To investigate whether deficiency of GM3 is involved in seizure susceptibility, we induced seizures with different chemoconvulsants in ST3GAL5 knockout mice. We report here that ST3GAL5 knockout mice are hyperactive and more susceptible to seizures induced by chemoconvulsants, including kainate and pilocarpine, compared with normal controls. In the hippocampal dentate gyrus, loss of GM3 aggravates seizure-induced aberrant neurogenesis. These data indicate that GM3 and gangliosides derived from GM3 may serve as important regulators of epilepsy and may play an important role in aberrant neurogenesis associated with seizures.

Etiology of Vision Loss in Ganglioside GM3 Synthase Deficiency

2006 ◽  
Vol 27 (3) ◽  
pp. 89-91 ◽  
Author(s):  
Fahhad Farukhi ◽  
Claudia Dakkouri ◽  
Heng Wang ◽  
Max Wiztnitzer ◽  
Elias I. Traboulsi
Keyword(s):  
Vision Loss ◽  
Ganglioside Gm3 ◽  
Gm3 Synthase

Effect of Ganglioside GM3 Synthase Gene Knockout on the GlycoproteinN-Glycan Profile of Mouse Embryonic Fibroblast

ChemBioChem ◽  
2012 ◽  
Vol 14 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Noriko Nagahori ◽  
Tadashi Yamashita ◽  
Maho Amano ◽  
Shin-Ichiro Nishimura
Keyword(s):  
Gene Knockout ◽  
Mouse Embryonic Fibroblast ◽  
Ganglioside Gm3 ◽  
Glycan Profile ◽  
Gm3 Synthase ◽  
Embryonic Fibroblast

Ganglioside GM3 is required for caffeic acid phenethyl ester-induced megakaryocytic differentiation of human chronic myelogenous leukemia K562 cells

2014 ◽  
Vol 92 (4) ◽  
pp. 243-249 ◽  
Author(s):  
Un-Ho Jin ◽  
Tae-Wook Chung ◽  
Kwon-Ho Song ◽  
Choong-Hwan Kwak ◽  
Hee-Jung Choi ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
K562 Cells ◽  
Caffeic Acid Phenethyl Ester ◽  
Camp Response Element Binding ◽  
Myelogenous Leukemia ◽  
Ganglioside Gm3 ◽  
Megakaryocytic Differentiation ◽  
Gm3 Synthase ◽  
Element Binding Protein ◽  
Characteristic Features

The human chronic myelogenous cell line K562 has been used extensively as a model for the study of leukemia differentiation. We show here that treatment of K562 cells with caffeic acid phenethyl ester (CAPE) induced a majority of cells to differentiate towards the megakaryocytic lineage. Microscopy analysis showed that K562 cells treated with CAPE exhibited characteristic features of physiological megakaryocytic differentiation, including the presence of vacuoles and demarcation membranes. Differentiation of K562 cells treated with CAPE was also accompanied by a net increase in megakaryocytic markers. The transcriptional activity of lactosylceramide α-2,3-sialyltransferase (GM3 synthase) and synthesis of ganglioside GM3 were increased by CAPE treatment. The promoter analysis of GM3 synthase demonstrated that CAPE induced the expression of GM3 synthase mRNA via activation of the cAMP response element-binding protein (CREB), transcription factor in nucleus. Interestingly, the inhibition of ganglioside GM3 synthesis by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol (D-PDMP) and GM3 synthase-siRNA blocked the CAPE-induced expression of the megakaryocytic markers and differentiation of K562 cells. Taken together, these results suggest that CAPE induces ganglioside GM3-mediated megakaryocytic differentiation of human chronic myelogenous cells.

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