Disease relevance of AIC-Riboside

• In rat cerebrocortical brain slices, AMPK was activated by metabolic stress (ischaemia > hypoxia > aglycaemia) and AICA riboside (0.1-10 mm) [1].
• In this paper we demonstrate that AICA riboside promotes apoptosis in undifferentiated human neuroblastoma cells (SH-SY5Y), inducing a raise in caspase-3 activity [2].
• Failure of AICA riboside to limit infarct size during acute myocardial infarction in rabbits [3].
• Besides that, at pH 7.45, the addition of 100 mumol/L AICA-riboside 5-amino-4-imidazolecarboxamide riboside, (an inhibitor of hepatic glycolysis) mimicked the effect of acidosis [4].
• Progressive cardiac dysfunction with repeated pacing-induced ischemia: protection by AICA-riboside [5].

High impact information on AIC-Riboside

• This study was designed to determine whether the increase in glucose uptake observed with AMPK activation by AICA-riboside is due to GLUT4 translocation from an intracellular location to the plasma membranes, similar to that seen in response to contraction [6].
• CONCLUSION/INTERPRETATION: Sustained activation of AMPK by AICA-riboside can trigger a caspase-dependent apoptosis of pancreatic beta cells [7].
• Beta cells isolated from AMPK-(alpha2)-deficient mice were resistant against AICA-riboside induced apoptosis [7].
• AMPK activation in beta cells was induced by the adenosine analog AICA-riboside and detected by immunoblotting using a phosphospecific antibody [7].
• AICA-riboside induces apoptosis of pancreatic beta cells through stimulation of AMP-activated protein kinase [7].

Chemical compound and disease context of AIC-Riboside

• Therefore, our results suggest that the toxic effect of AICA riboside on some types of neurons may participate in the neurological manifestations of syndromes related to purine dismetabolisms [8].

Biological context of AIC-Riboside

• A new cycloimidazole nucleoside, 5-(1 inch -benzamido-1 inch-hydroxymethylene) amino-2', 1 inch-anhydro-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (III) was synthesized by reaction of 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (AICA-riboside) with benzoyl isothiocyanate followed by methylation with methyl iodide [9].
• Apoptosis induction by AICA-riboside was also prevented by adding the MAPK-inhibitor SB203580 which blocked the AICA-riboside-induced phosphorylation of AMPK [7].
• AICA-riboside had no effect on glycolysis in cardiomyocytes, and a slight stimulatory effect in erythrocytes, but inhibited glycolysis by 65% at 250 microM concentration in FTO-2B cells, although only when tissue-culture medium was replaced by Krebs-Ringer bicarbonate buffer [10].
• The current studies suggest that AICA-Riboside could be used as a factor mediating renal cell mitosis in culture [11].
• In contrast, with concentrations above 100 microM of AICA-Riboside in the incubation medium, there was a remarkable inhibition of cell growth and a significant depletion of intracellular pools of adenine nucleotides and DNA [11].

Anatomical context of AIC-Riboside

• Perfusion medium containing AICA-riboside was found to significantly increase AMPK activity, glucose uptake, and GLUT4 translocation in skeletal muscle above basal levels [6].
• Meiotic induction by AICA riboside in dbcAMP-supplemented medium was initiated within 3 h in DO and 4 h in CEO and was accompanied by increased AMPK activity in the oocyte [12].
• AICA riboside also depressed excitatory synaptic transmission in area CA1 of the rat hippocampus, which was prevented by an adenosine A1 receptor antagonist and reversed by application of adenosine deaminase [1].
• AMPK activation was achieved by incubating FTO2B cells with AICA-riboside, which is transformed into ZMP, an AMP analogue, or by adenoviral transfection of hepatocytes with a constitutively active form of AMPK [13].
• Acadesine (AICA-riboside) is a purine nucleoside analog with anti-ischemic properties that is currently being studied (Phase 3) for the prevention of adverse cardiovascular outcomes in patients undergoing coronary artery bypass graft (CABG) surgery [14].

Associations of AIC-Riboside with other chemical compounds

• When 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICA riboside), an activator of AMPK, was tested on denuded oocytes (DO) and cumulus cell-enclosed oocytes (CEO) maintained in meiotic arrest by dbcAMP or hypoxanthine, GVB was dose-dependently induced [12].
• 5-Aminoimidazole-4-carboxamide riboside (AICA riboside; Acadesine) activates AMP-activated protein kinase (AMPK) in intact cells, and is reported to exert protective effects in the mammalian CNS [1].
• When AMPK is artificially activated with AICA riboside, ACC is inactivated, malonyl-CoA decreases, and fatty acid oxidation increases [15].

Gene context of AIC-Riboside

• Supplementation with AICA riboside lowered the levels of fixN expression in the purF mutants [16].
• Activation of AMPK by AICA riboside was greatly attenuated by inhibitors of equilibrative nucleoside transport [1].
• AICA riboside treatment of INS-1 cells, and of isolated rat islets, had both inhibitory and stimulatory effects on insulin secretion [17].
• In order to exert its effect on viability, AICA riboside must enter the cells and be phosphorylated to the ribotide, since both a nucleoside transport inhibitor, and an inhibitor of adenosine kinase produce an enhancement of the viability of AICA riboside-treated cells [2].
• Insulinotropic action of AICA riboside. I. Insulin release by isolated islets and the perfused pancreas [18].

Analytical, diagnostic and therapeutic context of AIC-Riboside

• Timely administration of AICA riboside reduces reperfusion injury in rabbits [19].
• AICA-riboside (375 mg) also was infused over 30 minutes before cardioplegia in the later group [20].
• A simple HPLC procedure for the quantitation of AICA-riboside (Z) and its 5-monophosphate metabolite (ZMP) in ultrafiltrates of plasma and lysed whole blood, respectively, has been developed [21].
• Resuscitation of hemorrhagic shock with hypertonic saline/dextran or lactated Ringer's supplemented with AICA riboside [22].

References