Abstract
NEU3 sialidase, a key enzyme in ganglioside metabolism, is activated under hypoxic conditions in cultured skeletal muscle cells (C2C12). NEU3 up-regulation stimulates the EGF receptor signaling pathway, which in turn activates the hypoxia-inducible factor (HIF-1α), resulting in a final increase of cell survival and proliferation. In the same cells, stable overexpression of sialidase NEU3 significantly enhances cell resistance to hypoxia, whereas stable silencing of the enzyme renders cells more susceptible to apoptosis. These data support the working hypothesis of a physiological role played by NEU3 sialidase in protecting cells from hypoxic stress and may suggest new directions in the development of therapeutic strategies against ischemic diseases, particularly of the cerebro-cardiovascular system.
MeSH terms
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Animals
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Apoptosis*
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Blotting, Western
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Caspases / metabolism
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Cell Hypoxia
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Cell Line
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Cell Proliferation
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Cytoprotection
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Enzyme Activation
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ErbB Receptors / metabolism*
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G(M3) Ganglioside / metabolism
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Gene Silencing
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Mice
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Models, Biological
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Muscle Cells / cytology*
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Muscle Cells / enzymology*
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Muscle, Skeletal / cytology*
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Neuraminidase / metabolism*
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Sialyltransferases / metabolism
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Signal Transduction
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Sp1 Transcription Factor / genetics
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Sp1 Transcription Factor / metabolism
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Sp3 Transcription Factor / genetics
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Sp3 Transcription Factor / metabolism
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Sphingolipids / metabolism
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Up-Regulation / genetics
Substances
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G(M3) Ganglioside
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Hypoxia-Inducible Factor 1, alpha Subunit
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Sp1 Transcription Factor
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Sphingolipids
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Sp3 Transcription Factor
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Sialyltransferases
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haematoside synthetase
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ErbB Receptors
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Neu3 protein, mouse
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Neuraminidase
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Caspases