Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.12 (chondroitinase)
 2,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucolipidosis IV (ML IV) (McKusick 252650) is an autosomal recessive metabolic disorder that displays signs of both lipid and mucopolysaccharide (glycosaminoglycan) storage. It has been reported that fibroblasts from ML IV patients exhibit abnormally high synthesis of hyaluronic acid in culture. In our search for a biochemical marker that will enable positive identification of ML IV, we studied glycosaminoglycan synthesis in fibroblast cultures from patients with this disease. ML IV and normal control fibroblasts were incubated with [3H]glucosamine and [35S]sulphate. Labelled glycosaminoglycans were extracted from the cell layer and medium. Chondroitin sulphate and hyaluronic acid were determined by analysis of disaccharides after digestion with chondroitinase ABC. Synthesis of neither of these two glycosaminoglycans differed significantly between control and ML IV fibroblasts. Synthesis of hyaluronic acid was nearly linear for 24 h, with mean calculated values of 11.7 +/- 1.4 and 14.4 +/- 1.6 pg/cell per 24 h in control and ML IV cultures respectively. The variability within the two groups is attributed primarily to population variability and possibly to culture density. These experiments exclude the possibility that a general metabolic defect in hyaluronic acid synthesis is responsible for the ML IV phenotype, nor can such a defect be used as a diagnostic tool for the disease.
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PMID:Mucolipidosis IV fibroblasts synthesize normal amounts of hyaluronic acid. 783 60

Advantage may be taken of macroautophagy ('autophagy') to promote ocular health. Autophagy continually captures aged or damaged cellular material for lysosomal degradation and recyling. When autophagic flux is chronically elevated, or alternatively deficient, health suffers. Chronic elevation of flux and stress are the consequence of inflammatory cytokines or of dry eye tears but not normal tears invitro. Exogenous tear protein lacritin transiently accelerates flux to restore homeostasis invitro and corneal health invivo, and yet the monomeric active form of lacritin appears to be selectively deficient in dry eye. Tissue transglutaminase-dependent cross-linking of monomer decreases monomer quantity and monomer affinity for coreceptor syndecan-1 thereby abrogating activity. Tissue transglutaminase is elevated in dry eye. Mutation of arylsulfatase A, arylsulfatase B, ceroid-lipofuscinosis neuronal 3, mucolipin, or Niemann-Pick disease type C1 respectively underlie several diseases of apparently insufficient autophagic flux that affect the eye, including: metachromatic leukodystrophy, mucopolysaccharidosis type VI, juvenile-onset Batten disease, mucolipidosis IV, and Niemann-Pick type C associated with myelin sheath destruction of corneal sensory and ciliary nerves and of the optic nerve; corneal clouding, ocular hypertension, glaucoma and optic nerve atrophy; accumulation of 'ceroid-lipofuscin' in surface conjunctival cells, and in ganglion and neuronal cells; decreased visual acuity and retinal dystrophy; and neurodegeneration. For some, enzyme or gene replacement, or substrate reduction, therapy is proving to be successful. Here we discuss examples of restoring ocular surface homeostasis through alteration of autophagy, with particular attention to lacritin.
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PMID:Lacritin and other autophagy associated proteins in ocular surface health. 2631 8