Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysosomal sialidase, encoded by neu1, is required for the removal of terminal sialic acid residues from a variety of sialoglycoconjugates. In humans, deficiency of this enzyme results in the inborn error of metabolism sialidosis, characterized by the accumulation of sialoglycoconjugates within the nervous system and in peripheral organs. A subset of sialidosis patients present with symptoms of profound muscle dysfunction, including progressive muscular atrophy. We have previously shown that the 5' regulatory region of murine neu1 is typical of skeletal muscle-specific genes due to the presence of several E-boxes and its responsiveness to stimulation by muscle regulatory factors (MRFs) such as MyoD. Here, we report that sialidase activity is increased 6-fold during the first 24 h of differentiation of C2C12 myoblasts followed by an attenuation to pre-differentiation levels by 48 h. We demonstrate that the lysosomal sialidase promoter is highly upregulated by MyoD through a mechanism that is dependent on the MyoD chromatin remodeling domain. We also show that the sialidase promoter is repressed by activated MEK. Inappropriate overexpression of sialidase 48 h after the onset of differentiation results in downregulation of myogenin as well as myosin heavy chain expression and in a halt of the differentiation cascade. This study indicates that lysosomal sialidase is a potent regulator of the early stages of myogenesis.
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PMID:Overexpression of MyoD-inducible lysosomal sialidase (neu1) inhibits myogenesis in C2C12 cells. 1621 42

Neuraminidase-1 (NEU1) is the sialidase responsible for the catabolism of sialoglycoconjugates in lysosomes. Congenital NEU1 deficiency causes sialidosis, a severe lysosomal storage disease associated with a broad spectrum of clinical manifestations, which also include skeletal deformities, skeletal muscle hypotonia and weakness. Neu1(-/-) mice, a model of sialidosis, develop an atypical form of muscle degeneration caused by progressive expansion of the connective tissue that infiltrates the muscle bed, leading to fiber degeneration and atrophy. Here we investigated the role of Neu1 in the myogenic process that ensues during muscle regeneration after cardiotoxin-induced injury of limb muscles. A comparative analysis of cardiotoxin-treated muscles from Neu1(-/-) mice and Neu1(+/+) mice showed increased inflammatory and proliferative responses in the absence of Neu1 during the early stages of muscle regeneration. This was accompanied by significant and sequential upregulation of Pax7, MyoD, and myogenin mRNAs. The levels of both MyoD and myogenin proteins decreased during the late stages of regeneration, which most likely reflected an increased rate of degradation of the myogenic factors in the Neu1(-/-) muscle. We also observed a delay in muscle cell differentiation, which was characterized by prolonged expression of embryonic myosin heavy chain, as well as reduced myofiber cross-sectional area. At the end of the regenerative process, collagen type III deposition was increased compared to wild-type muscles and internal controls, indicating the initiation of fibrosis. Overall, these results point to a role of Neu1 throughout muscle regeneration.
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PMID:Neuraminidase-1 mediates skeletal muscle regeneration. 2600 31