Further Characterization of Equine Brain Gangliosides: The Presence of GM3 Having N-Glycolyl Neuraminic Acid in the Central Nervous System

Mikami, Takeshi; Kashiwagi, Motoi; Tsuchihashi, Keiko; Daino, Takumi; Akino, Toyoaki; Gasa, Shinsei

doi:10.1093/oxfordjournals.jbchem.a021962

Cited by 23 publications

(18 citation statements)

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“…Relative Absence of Neu5Gc Is a Conserved Feature of Vertebrate Brain-Prior studies of sialic acids in the vertebrate brain have either failed to find Neu5Gc or reported it to be present only at very low levels (10,26,(81)(82)(83)(84)(85)(86)(87)(88). To confirm and extend these findings, we collected samples of brain tissue from chimpanzee, mouse, rat, cow, pig, and dolphin.…”

Section: Resultsmentioning

confidence: 81%

Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups

Davies

Pearce

Tessier

et al. 2012

Journal of Biological Chemistry

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Background:The sialic acid N-glycolylneuraminic acid (Neu5Gc) shows conserved suppression of expression in vertebrate brains, suggesting brain-specific toxicity. Results: ␣2-8-Linked Neu5Gc incorporated into the neural glycan polysialic acid (polySia) resists sialidase breakdown through conformational effects. Conclusion: Neu5Gc in brain would prevent rapid turnover of surface polySia. Significance: This mechanism potentially underlies the evolutionary suppression of Neu5Gc expression in vertebrate brains.

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Section: Resultsmentioning

confidence: 81%

Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups

Davies

Pearce

Tessier

et al. 2012

Journal of Biological Chemistry

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“…It remains to be seen whether the mutation in CMP-sialic acid hydroxylase can explain some of the dramatic morphological and functional changes that occurred during the evolution of humans. In this regard, perhaps the most intriguing observation is that no matter what the level of Neu5Gc was in other parts of the body, the amounts in the brain were always very low in a variety of animals studied (34)(35)(36), including the chimpanzee (37). This correlates with very low levels of hydroxylase message in the mouse brain (45).…”

Section: Discussionmentioning

confidence: 99%

“…The conversion from Neu5Ac to Neu5Gc can positively or negatively affect interactions involving several of the known endogenous and exogenous receptors for sialic acids such as CD22, myelin-associated glycoprotein, sialoadhesin, and the influenza A virus hemagglutinin (27)(28)(29)(30)(31)(32)(33). Interestingly, even in animals with large amounts of Neu5Gc in other tissues, its level in the brain is always extremely low (34)(35)(36). We recently reported a major biochemical difference between the great apes and humans, with the latter showing a loss of activity of the enzyme CMP-N-acetylneuraminic acid hydroxylase (37).…”

mentioning

confidence: 99%

A mutation in human CMP-sialic acid hydroxylase occurred after theHomo-Pandivergence

Chou

Takematsu

Díaz

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

531

432

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Sialic acids are important cell-surface molecules of animals in the deuterostome lineage. Although humans do not express easily detectable amounts of N-glycolylneuraminic acid (Neu5Gc, a hydroxylated form of the common sialic acid N-acetylneuraminic acid, Neu5Ac), it is a major component in great ape tissues, except in the brain. This difference correlates with lack of the hydroxylase activity that converts CMP-Neu5Ac to CMP-Neu5Gc. Here we report cloning of human and chimpanzee hydroxylase cDNAs. Although this chimpanzee cDNA is similar to the murine homologue, the human cDNA contains a 92-bp deletion resulting in a frameshift mutation. The isolated human gene also shows evidence for this deletion. Genomic PCR analysis indicates that this deletion does not occur in any of the African great apes. The gene is localized to 6p22-p23 in both humans and great apes, which does not correspond to known chromosomal rearrangements that occurred during hominoid evolution. Thus, the lineage leading to modern humans suffered a mutation sometime after the common ancestor with the chimpanzee and bonobo, potentially affecting recognition by a variety of endogenous and exogenous sialic acid-binding lectins. Also, the expression of Neu5Gc previously reported in human fetuses and tumors as well as the traces detected in some normal adult humans must be mediated by an alternate pathway.

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“…Expression of Neu5Gc in the mammalian brain is very low, even in species like the mouse and chimpanzee, in which expression in other tissues can be high (26,29,37). Here we show that this is true even in the fetal state (note the negative staining of the brain in the WT fetal sections in Fig.…”

Section: Vol 27 2007 N-glycolylneuraminic Acid Deficiency In Mice 4343mentioning

confidence: 99%

N-Glycolylneuraminic Acid Deficiency in Mice: Implications for Human Biology and Evolution

Hedlund

Tangvoranuntakul

Takematsu

et al. 2007

Molecular and Cellular Biology

185

211

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Humans and chimpanzees share >99% identity in most proteins. One rare difference is a human-specific inactivating deletion in the CMAH gene, which determines biosynthesis of the sialic acid N-glycolylneuraminic acid (Neu5Gc). Since Neu5Gc is prominent on most chimpanzee cell surfaces, this mutation could have affected multiple systems. However, Neu5Gc is found in human cancers and fetuses and in trace amounts in normal human tissues, suggesting an alternate biosynthetic pathway. We inactivated the mouse Cmah gene and studied the in vivo consequences. There was no evidence for an alternate pathway in normal, fetal, or malignant tissue. Rather, null fetuses accumulated Neu5Gc from heterozygous mothers and dietary Neu5Gc was incorporated into oncogene-induced tumors. As with humans, there were accumulation of the precursor N-acetylneuraminic acid and increases in sialic acid O acetylation. Null mice showed other abnormalities reminiscent of the human condition. Adult mice showed a diminished acoustic startle response and required higher acoustic stimuli to increase responses above the baseline level. In this regard, histological abnormalities of the inner ear occurred in older mice, which had impaired hearing. Adult animals also showed delayed skin wound healing. Loss of Neu5Gc in hominid ancestors ϳ2 to 3 million years ago likely had immediate and long-term consequences for human biology.

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Further Characterization of Equine Brain Gangliosides: The Presence of GM3 Having N-Glycolyl Neuraminic Acid in the Central Nervous System

Cited by 23 publications

References 0 publications

Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups

Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups

A mutation in human CMP-sialic acid hydroxylase occurred after theHomo-Pandivergence

N-Glycolylneuraminic Acid Deficiency in Mice: Implications for Human Biology and Evolution

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