Disease relevance of N-METHYLDEOXYNOJIRIMYCIN

• CONCLUSIONS: Preischemic treatment with MOR-14 preserved glycogen, attenuated the accumulation of lactate, and reduced the myocardial infarct size by 69% [1].
• Another 40 rabbits given 100 mg of MOR-14 or saline 10 minutes before ischemia were euthanized at 10 or 30 minutes of ischemia for biochemical analysis [1].
• To assess the infarct size-reducing effect of MOR-14, 54 rabbits were subjected to 30-minute coronary occlusion followed by 48-hour reperfusion [1].
• The fowl plague virus glycoproteins in N-methyl-1-deoxynojirimycin-treated cells contain oligosaccharides of the composition Glc3ManxGlcNAc2 (x = 7, 8, and 9) [2].
• Preischemic treatment with MOR-14 is protective against postischemic left ventricular dysfunction through the inhibition of glycogenolysis in the isolated rat heart [3].

High impact information on N-METHYLDEOXYNOJIRIMYCIN

• SM-FeSV-transformed cells treated with the glucosidase-I inhibitors N-methyldeoxynojirimycin (MdN) or castanospermine synthesized predominantly a gp125v-fms species which had a normal half life [4].
• Thus, we investigated whether MOR-14 could inhibit alpha-1,6-glucosidase and reduce the infarct size in rabbit hearts without collateral circulation [1].
• Preischemic treatment with 25, 50, and 100 mg/kg of MOR-14 dose-dependently reduced the infarct size (to 26+/-4%, 19+/-3%, and 14+/-2% of the area at risk, respectively), compared with the saline control (45+/-5%) without altering the blood pressure or heart rate [1].
• In contrast, two glucosidase I inhibitors (castanospermine [CA] and N-methyl-1-deoxynojirimycin [MdN]) blocked carbohydrate remodeling at an early stage within the endoplasmic reticulum and prevented cell surface expression of v-fms proteins [5].
• Castanospermine and the glucosidase inhibitor N-methyldeoxynojirimycin prevented the morphological differentiation of endothelial cells in vitro [6].

Biological context of N-METHYLDEOXYNOJIRIMYCIN

• The reduced maximal transport to the cell surface observed with N-methyl-1-deoxynojirimycin may suggest that proper glycosylation is necessary for an efficient transport from the Golgi apparatus to the microvillar membrane [7].
• Taken as a whole, our data suggest that PKC acts downstream of the inhibition of glycogenolysis by MOR-14 to reduce infarct size [8].
• In contrast, urinary clearance of N-methyl-1-deoxynojirimycin was two to three times higher than the glomerular filtration rate, indicating active tubular secretion [9].
• The mannosidase IA/B inhibitor 1-deoxymannojirimycin and the glucosidase inhibitor N-methyl-1-deoxynojirimycin exhibited minimal plasma protein binding and showed a rapid biphasic plasma disappearance, with an initial t1/2 of 3.0 and 4.5 min, respectively, and a terminal t1/2 of 51 and 32 min, respectively [9].

Anatomical context of N-METHYLDEOXYNOJIRIMYCIN

• The alpha-glucosidase inhibitor N-methyl-1-deoxynojirimycin (MDJN) inhibits the synthesis of N-linked complex oligosaccharides in rat intestinal epithelial cells to the same extent as reported previously for 1-deoxynojirimycin (DJN) [Saunier, Kilker, Tkacz, Quaroni & Herscovics (1982) J. Biol. Chem. 257, 14155-14161] [10].
• The glucosidase inhibitors 1-deoxynojirimycin, N-methyl-1-deoxynojirimycin and castanospermine were used to inhibit oligosaccharide processing in primary cultures of rat hepatocytes [11].
• The effect of the glucosidase inhibitors N-methyl-1-deoxynojirimycin (MDJN) and bromoconduritol on the adhesion of chick myoblasts and rat L6 myoblasts to fibronectin and laminin was compared with that of the mannosidase I inhibitor, 1-deoxymannojirimycin (ManDJN) [12].
• For this purpose, murine hybridoma cells secreting an anti beta-lactoglobulin IgE were incubated either in the presence of inhibitors of glucosidase I (castanospermine or N-methyl-1-deoxynojirimycin), or of an inhibitor of Golgi mannosidase II (swainsonine) [13].
• This enhancement of ChAT activity was not observed in the presence of concanavalin A (ConA) or N-methyl-1-deoxynojirimycin (MDJN) which inhibits myoblast fusion, creatine phosphokinase and acetylcholinesterase activities in muscle cells [14].

Associations of N-METHYLDEOXYNOJIRIMYCIN with other chemical compounds

• Preischaemic treatment with N-methyl-1-deoxynojirimycin (MOR-14), an alpha-1,6-glucosidase inhibitor, attenuates glycogenolysis and lactate accumulation during ischaemia and markedly reduces infarct size in rabbit hearts [8].

Gene context of N-METHYLDEOXYNOJIRIMYCIN

• Treatment of cultured skin fibroblasts for 7 days with N-methyldeoxynojirimycin, a potent inhibitor of the endoplasmic reticulum processing enzymes glucosidase I and II, resulted in an accumulation of the same Man5GlcNAc2-PP-dolichol species that was elevated in juvenile NCL brain [15].
• Inhibition of glucosidases I and II by castanospermine or N-methyldeoxynojirimycin delayed the vitronectin receptor alpha/beta chain heterodimer assembly and alpha chain cleavage and resulted in a decrease in the level of expression cell surface receptor [16].

Analytical, diagnostic and therapeutic context of N-METHYLDEOXYNOJIRIMYCIN

• Infarct size, as a per cent of area at risk, was significantly smaller in rabbits administered 100 mg kg(-1) of MOR-14 10 min before ischaemia (17+/-2%, n=10), than in a control group (46+/-5%, n=10) [8].
• Combination of N-methyl-1-deoxynojirimycin and ischemic preconditioning markedly reduces the size of myocardial infarcts in rabbits [17].

References