Disease relevance of Aga

• Aspartylglucosaminuria (AGU) is a neurodegenerative lysosomal storage disease that is caused by mutations in the gene encoding for a soluble hydrolase, aspartylglucosaminidase (AGA) [1].
• A full-length insert for the Flavobacterium meningosepticum N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase gene was located on a 2500-bp HindIII fragment and cloned into the plasmid vector pBluescript [2].
• The Flavobacterium glycosylasparaginase gene was expressed in Escherichia coli and found to be enzymatically active [2].

High impact information on Aga

• Expression and endocytosis of lysosomal aspartylglucosaminidase in mouse primary neurons [1].
• Structural modelling suggests that Gliap is an atypical mammalian type-I asparaginase inasmuch as it harbours the active centre of a type-I glycosylasparaginase but, like plant-type asparaginases, lacks their auto-proteolytic site and, in addition, exhibits significant type-II L-asparaginase enzymatic activity [3].
• Impaired intercellular coupling caused either by the loss of connexin 43 or by treatment of cultured embryos with the gap junctional coupling blocker 18alpha-glycyrrhetinic acid (AGA) had no discernable effect on either apoptosis or glucose utilization, parameters known to be affected by gap junctional coupling in other contexts [4].
• Blockade of L-type Ca2+ channels by 5 microM nifedipine or Q-type Ca2+ channels by 2 microM Aga IVA reduced BK current activation by 77 and 42%, respectively [5].
• The DHP agonist Bay K 8644 (5 microM) produced a 36% increase in ICa in a similar proportion of CeA neurons (70%). omega-Conotoxin GVIA (CgTx GVIA, 1 microM) in saturating concentrations inhibited 30% of ICa, whereas omega-agatoxin IVA (Aga IVA, 100 nM), in concentrations known to block P-type currents, did not affect ICa [6].

Anatomical context of Aga

• MATERIALS AND METHODS: The glutaraldehyde-fixed acellular pericardium (AGA), the genipin-fixed cellular pericardium (GP), and a commercially available polypropylene mesh were used as controls [7].
• In contrast, host cells (inflammatory cells, fibroblasts, and neo-capillaries) were able to infiltrate into the AGA and AGP patches [7].
• AGA stimulated gastric mucus secretion and prevented the increment of back-diffusion of hydrogen ion into the mucosa significantly [8].
• AGA at the cytoprotective doses caused almost no decrease of the gastric acid secretion in both pylorus-ligated and non-ligated rats [8].
• These data indicate that AGA caused a cytoprotective effect not through the suppression of acid secretion but through the augmentation of the defense of the mucosa against autodigestion by gastric juice [8].

Associations of Aga with chemical compounds

• The O, P and Q-type VDCC inhibitor, omega-agatoxin IVA (Aga IVA, 1 microM), blocked 100% of GABA and glutamate, 70% of DA and about 50% of 5-HT and ACh release [9].
• The VDCC blockers omega-AGA-IVA (AGA), omega-conotoxin GVIA (GVIA), omega-conotoxin MVIIC (MVIIC) and nimodipine (NIM) were assessed for their ability to inhibit monosynaptic EPSCs and IPSCs [10].
• The preventive effect of AGA against taurocholate-induced lesions was more marked than that against the other two noxious agents [8].
• In addition, pretreatment with indomethacin diminished the cytoprotective effect of AGA almost completely [8].
• Rat liver glycosylasparaginase (N4-(beta-N-acetyl-D-glucosaminyl)-L-asparagine amidohydrolase (EC 3.5.1.26) was irreversibly inhibited in vitro by the asparagine analogue 5-diazo-4-oxo-L-norvaline (DONV) [11].

Analytical, diagnostic and therapeutic context of Aga

• In both cell types, pharmacological dissection using selective VDCC inhibitors, omega-agatoxin IVA (Aga IVA), omega-conotoxin GVIA (GVIA) and nifedipine demonstrated the existence of P/Q-, N- and L-type VDCC, respectively [12].
• Molecular cloning and sequence analysis of Flavobacterium meningosepticum glycosylasparaginase: a single gene encodes the alpha and beta subunits [2].

References