Disease relevance of iodoacetate

• Unexpectedly, we found that after 'chemical hypoxia' with cyanide and iodoacetate, cytosolic free Ca2+ does not change during bleb formation or before loss of cellular viability [1].
• Either inhibition or enhancement of the spontaneous lymphoma exhibited by AKR mice was observed after treatment with different dosages of the sulfhydryl inhibitor, sodium iodoacetate [2].
• Pretreatment with iodoacetate significantly advanced these events (1.9 +/- 0.7, 3.6 +/- 0.9, and 1.9 +/- 0.2 minutes of ischemia, respectively) [3].
• The results indicated that HPD-induced photosensitization had little additive effects to oligomycin-sensitive ATP production, whereas significant further reduction in ATP levels was obtained by HPD-induced photosensitization in the presence of iodoacetate [4].
• Exposure of cultured hepatoma 1c1c7 cells to KCN and iodoacetate, to produce chemical anoxia, caused a rapid and sustained increase in cytosolic-free Ca2+ concentration, which was associated with depletion of intracellular ATP and glutathione [5].

Psychiatry related information on iodoacetate

• We have previously shown that memory processing for bead discrimination learning is dependent on glycolysis; however, the metabolic inhibitor used, iodoacetate, inhibits pyruvate formation from both glucose and glycogen [6].
• The faster response times in IAA and IA groups were independent of the size of the workload jump, and the increase in myocardial oxygen consumption during workload steps was unaffected by CK or glycolysis blockade [7].

High impact information on iodoacetate

• Despite the fact that glycolytic flux had been blocked both by iodoacetate and by absence of substrate, end-diastolic left ventricular pressure (EDP) remained unchanged (P > 0.15, n = 6) [8].
• Glycogen was effectively depleted after 15-min perfusion with glucagon (2 mg/liter), as verified by the lack of rise in [SP] during exposure to iodoacetate (100 microM) in substrate-free perfusate [8].
• This study was initiated to characterize the effects of synthetic inhibitors of phospholipase activities using a cultured myocardial cell model in which arachidonic acid is liberated after treatment with the metabolic inhibitor, iodoacetate [9].
• Inhibiting glycolysis with iodoacetate (IAA) (10(-3)M) had a much smaller suppressant effect on tension (28 +/- 24%) but markedly increased [K+]0 accumulation (by 1.8 +/- 1.1 mM) at 10 min [10].
• The shortening of action potential duration was not significantly different for the four interventions. pH0 increased slightly during IAA (+0.04-+0.06 U) and fell during the other interventions (-0.10--0.16 U), but this did not account for the differences in [K+]0 accumulation and tension between inhibition of glycolytic vs. oxidative metabolism [10].

Chemical compound and disease context of iodoacetate

• Approximately 2.4 of the 4 cysteine residues of FNR can be alkylated with iodoacetate in permeabilized aerobic or anaerobic bacteria without the addition of reducing agents [11].
• Removal of extracellular glucose, hypoxia, cyanide and monoiodoacetate almost completely inhibit the secretion [12].
• Similar time-dependent periodic changes of uptake rates also occurred during incubation of C6 glioma cells with 2 mM 2-deoxyglucose (2-DG) without pretreatment of the cells with iodoacetate [13].
• We have quantified and correlated the onset of contracture with levels of ATP and glycogen during cold storage in rabbit hearts flushed with UW solution, with and without 1 mM calcium (Ca), or 3 mM iodoacetate (IAA) [14].
• Change of cytosolic calcium in CA1 neurons during application of N-methyl-D-aspartate (NMDA) was measured, as were calcium changes during simulated ischemia (hypoxia, NaCN, iodoacetate) of hypoxia plus high glutamate concentration (pO2 = 25 mmHg, 3 mM glutamate) [15].

Biological context of iodoacetate

• Inhibition of lung oxygen consumption by iodoacetate is associaged with a dose-dependent inhibition of the pilocarpine-induced secretion [16].
• The circulatory effects of selective metabolic inhibition of glycolysis and of the tricarboxylic acid cycle by iodoacetate and fluoroacetate were studied in intact chloralose-anesthetized dogs [17].
• The protein, a homodimer of 57-kDa subunits, was shown to contain selenium in the form of selenocysteine; hydrolysis of the protein alkylated with either iodoacetate or 3-bromopropionate yielded Se-carboxymethyl-selenocysteine or Se-carboxyethyl-selenocysteine, respectively [18].
• In contrast, modification with IAA of m3G-capped U1 snRNPs reconstituted in vitro did not interfere with their nuclear transport in oocytes [19].
• These findings suggest that the administration of iodoacetate potentiated the immunocompetence of bone marrow by affecting thymus-derived cells [20].

Anatomical context of iodoacetate

• In general, splenic lymphocytes harvested from mice given a single 0.01-mg treatment of iodoacetate were not as reactive as were control cell cultures when exposed to the T-cell mitogens [2].
• Since present methods for the isolation of heterokaryons are unsuitable for the selection of hybrids between whole cells and anucleate cytoplasms (heteroplasmons), a selective system has been developed which is based on the capacity of anucleate cytoplasms containing active enzymes to rescue whole cells poisoned with iodoacetate [21].
• Thiol oxidation is unlikely to promote GAPDH binding, since perfusion with iodoacetate under aerobic conditions or treatment of homogenates with N-ethylmaleimide or diamide failed to induce GAPDH association with the myofibrils [22].
• IAA modification of m7G-capped U1 snRNPs inhibited hypermethylation when they were microinjected into Xenopus oocytes and consequently also inhibited nuclear import [19].
• Induction of metallothionein-I mRNA in cultured cells by heavy metals and iodoacetate: evidence for gratuitous inducers [23].

Associations of iodoacetate with other chemical compounds

• Dinitrophenol, however, in combination with NaF or iodoacetate decreased DDP accumulation [24].
• Pretreatment of the cells with the Ca2+ chelators Quin 2 or BAPTA markedly delayed both the onset of blebbing and loss of cell viability, but did not affect KCN- and iodoacetate-induced loss of ATP and glutathione [5].
• Glucosamine, 2-deoxyglucose, phloridzin, and iodoacetic acid blocked the activation of glucose-responsive neurons by the transition from 5 to 20 mmol/l glucose [25].
• Superoxide generation was inhibited by 2-deoxy-D-glucose (ID50 4 X 10(-5)M), 2-iodoacetate (ID50 5 X 10(-5)M), and N-ethyl-maleimide (ID50 5 X 10(-6)M), suggesting a dependence on anaerobic glycolysis and sulfhydryl groups [26].
• The 8-mercapto-FAD reconstituted into the cytochrome reacted readily with either iodoacetamide (k = 38.8 M-1.min-1) or iodoacetic acid (k = 12.1 M-1.min-1) to give a fluorescence spectrum characteristic of a 8-mercaptoflavin derivative, 8-SCH2CONH2 FAD or 8-SCH2COOH FAD [27].

Gene context of iodoacetate

• In addition, we determined whether the inhibition of GAPDH with iodoacetate induces dysmorphogenesis, analogous to that caused by high glucose concentration, and whether antioxidants modulated the putative teratogenic effect of such direct GAPDH inhibition [28].
• Thus, the inhibitory effect of the M-DSP on 5-LO could be overcome by the GPx-1 inhibitor mercaptosuccinate and by the broad spectrum GPx inhibitor iodoacetate, as well as by addition of 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13(S)-HPODE) [29].
• Pretreatment with the glycolytic inhibitor iodoacetic acid caused a remarkable reduction of Na,K-ATPase activity, whereas pretreatment with the oxidative inhibitor carbonyl cyanide m-chlorophenylhydrazone caused no detectable changes, suggesting that the phosphorylated cofilin is involved in feeding glycolytic fuel for Na,K-ATPase activity [30].
• Complex formation is complete after 4 h and is inhibited by pretreating alpha 2M with dithiothreitol, iodoacetamide, iodoacetic acid, and N-ethylmaleimide [31].
• CA IX changes under severe hypoxia and the inhibitory effect of the glycolysis inhibitor iodoacetate (IAA, 50 microM) on hypoxic CA IX overexpression were paralleled by the results for HIF-1alpha protein [32].

Analytical, diagnostic and therapeutic context of iodoacetate

• Sustained ischemia was induced in three experimental groups: (1) control, (2) preparations preconditioned with two 5-minute periods of ischemia followed by reperfusion, and (3) preparations pretreated with 1 mmol/L iodoacetate to block anaerobic metabolism and minimize acidification during ischemia [3].
• The aim of this study was to evaluate changes in the subcellular organelles of cultured hepatocytes by laser scanning confocal microscopy during chemical hypoxia with cyanide and iodoacetate, inhibitors of mitochondrial respiration and glycolysis, respectively [33].
• Low-light digitized video fluorescence polarization microscopy was used to measure lipid order parameters in plasma membrane blebs of single, cultured rat hepatocytes during ATP depletion with the metabolic inhibitors cyanide and iodoacetic acid [34].
• The present study examines the in vivo effect of triamcinolone hexacetonide on the degeneration of articular cartilage which occurs following intraarticular injection of sodium iodoacetate [35].
• IAA/IAF-enzyme was digested by extensive trypsinolysis, and the fluorescent peptides released from the membrane were purified by high performance liquid chromatography and sequenced [36].

References