Aurin tricarboxylic acid, the anti-AIDS compound, prevents the binding of interferon-α to its receptor

Gan, Yuxiang; Weaver, James L.; Pine, P. Scott; Zoon, Kathryn C.; Aszalós, Adorján

doi:10.1016/0006-291x(90)91590-o

Cited by 17 publications

(9 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, if ATA does cross the plasma membrane, its effect on metabolic enzymes may prove detrimental to the cell. Among its known extracellular actions, ATA reduces infectivity of HIV by blocking the gpl20 viral coat protein from interacting with the CD4 receptor , prevents binding of interferon-a to its receptor (Gan et al, 1990), and, as demonstrated here, antagonizes NMDA receptor activity. Thus, any demonstrated protection by ATA versus cell death needs to be evaluated in light of its multitude of actions and ability to enter cells.…”

Section: Discussionmentioning

confidence: 57%

Aurintricarboxylic Acid Prevents NMDA‐Mediated Excitotoxicity: Evidence for Its Action as an NMDA Receptor Antagonist

Zeevalk¹,

Schoepp

Nicklas³

1993

Journal of Neurochemistry

View full text Add to dashboard Cite

The effect of the endonuclease inhibitor aurintricarboxylic acid (ATA) versus NMDA-mediated delayed cell death was examined in an ex vivo chick retinal preparation. Transient exposure to 100 microM NMDA for 60 min followed by a 24-h recovery period resulted in a sevenfold increase in lactate dehydrogenase (LDH) release into the medium. ATA at 100 microM significantly reduced NMDA-mediated LDH release by 60%. In clarifying the mechanism of protection versus NMDA, ATA was found to inhibit several acute NMDA-mediated effects: ATA attenuated NMDA-mediated GABA release in a dose-dependent manner (IC50 = 29.5 microM), prevented NMDA-stimulated cyclic GMP formation, and blocked NMDA-mediated 22Na+ influx. These acute inhibitory effects of ATA were overcome by increasing the NMDA concentration, which suggested a competitive interaction between NMDA and ATA. In a binding assay using membranes prepared from adult rat forebrain, ATA displaced the competitive NMDA receptor ligand [3H]CGS 19755 with an IC50 of 26.9 microM. Maximal displacement was 88% with 100 microM ATA. These studies demonstrate that ATA protected neurons from NMDA-mediated cell death upstream of endonuclease inhibition, i.e., by antagonizing NMDA receptor activity in a manner consistent with competitive antagonism.

show abstract

Section: Discussionmentioning

confidence: 57%

Aurintricarboxylic Acid Prevents NMDA‐Mediated Excitotoxicity: Evidence for Its Action as an NMDA Receptor Antagonist

Zeevalk¹,

Schoepp

Nicklas³

1993

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Therefore, scaffolds with meta and/or mixed ortho-meta linkages and extensive branches are not substantially incorporated into polymers 6-12. The appearance of benzylic carbon resonances (30)(31)(32)(33)(34) ppm) suggest that the polymerization occurred through repetitive electrophilic aromatic substitution reactions. No signals were observed that would indicate substantial coupling of the polymer had occurred through benzyl phenyl ether bonds.…”

Section: Resultsmentioning

confidence: 98%

“…These include aurintricarboxylic acid (ATA), 3 ( Figure 1) [9][10][11][12], poly(9-vinyladenine) [13], poly(l-vinyluracil) [13], pyran copolymer [14], chloramphenicol ester of maleic acid and 10-undecendyl copolymer [15], poly-N-oxides [16], copolymer with formaldehyde and sulfapyridine [17], copolymer with urea and formaldehyde [18] and polyacrylamide sialic acid copolymer [19]. ATA has been extensively studied and exhibits a variety of biological activities including the inhibition of enzynies binding to nucleic acids (DNA polymerase [20][21][22], RNA polymerase [23][24][25], ribonucleases [26][27][28]), the inhibition of ristocetin or shear stress induced vWF mediated platelet aggregation [29,30], inhibition of cytopathic effects of HIV 1 [31], prevention of binding of interferon to its receptor [32] and binding to polynucleotide domains of glucocorticoid receptors [33] and dihydroxyvitamin D3 receptors [34].…”

mentioning

confidence: 99%

Mimicry of Biological Macromolecules by Polyaromatic Anionic Compounds

Regan¹,

Bruno²,

Chang³

et al. 1993

Journal of Bioactive and Compatible Polymers

View full text Add to dashboard Cite

The preparation, characterization and biological properties of some polyanionic polymers are reported. These polymers are constructed with repeating phenol-based monomers. The anionic groups attached to the aromatic nucleus provide the basis for binding to basic domains of proteins. Scaf-*Author to whom correspondence should be addressed.at CARLETON UNIV on June 21, 2015 jbc.sagepub.com Downloaded from 318 fold flexibility permits the polyanionic polymers to adopt low energy conformations suitable for interacting with coagulation proteins and an anti-DNA monoclonal antibody. Structure activity relationships (SAR) and comparisons with aurintricarboxylic acid are described. The polymers doubled the clotting time in the APTT assay with value ranging from 10-1000 μg/mL. Binding to an anti-DNA monoclonal antibody occurred with ICso values of 0.3-5.0 μg/mL. INTRODUCTIOÑ

show abstract

“…The inhibitory action of IFN-␣ on clock-gene expression was blocked by treatment with ATA. ATA is a triphenylmethane derivative that competes with the binding of IFN-␣ to its specific receptor, thereby preventing the phosphorylation of STAT1 and STAT2 proteins (Gan et al, 1990;Grimley et al, 1998). Therefore, the present results indicate that the inhibitory effect of IFN-␣ on the mRNA expression of Clock and Bmal1 is elicited by activation of the JAK-STAT signaling pathway; thus, there may be a link between the downstream of IFN-␣ signal transduction and the circadian biological clock system.…”

Section: Alteration Of Biological Rhythms Induced By Interferon-␣ 1397mentioning

confidence: 99%

Alteration of Intrinsic Biological Rhythms during Interferon Treatment and Its Possible Mechanism

Koyanagi

Ohdo

2002

Mol Pharmacol

View full text Add to dashboard Cite

One of the most indispensable biological functions for all living organisms is the circadian clock, which acts like a multifunctional timer to regulate the homeostatic system, including sleep and wakefulness, hormonal secretions, and various other bodily functions with a 24-h cycle. We reported previously that interferon (IFN) has the ability to modulate the biological clock system at the genetic level. In the present study, this mechanism was investigated further by evaluating the effects of IFN-␣ on circadian output function. Treatment of cultured hepatic cells (HepG2) with IFN-␣ significantly decreased the protein levels of CLOCK and BMAL1, which are positive regulators of circadian output rhythm, then their mRNA levels. Aurintricarboxylic acid, a ligand inhibitor of IFN-␣, dose dependently inhibited the IFN-␣-induced phosphorylation of the signal transducer and activator of transcription 1 (STAT1) protein in HepG2 cells, accompanied by the restoration of Clock and Bmal1 mRNA levels. The continuous administration of IFN-␣ significantly decreased CLOCK and BMAL1 protein levels in the suprachiasmatic nucleus and liver of mice, thereby preventing oscillations in the expression of clock and clock-controlled output genes. These results reveal a possible pharmacological action by IFN-␣ on the core circadian oscillation mechanism and indicate that the disruptive effect of IFN-␣ on circadian output function is the underlying cause of its adverse effects on 24-h rhythms in physiology and behavior.

show abstract

Aurin tricarboxylic acid, the anti-AIDS compound, prevents the binding of interferon-α to its receptor

Cited by 17 publications

References 9 publications

Aurintricarboxylic Acid Prevents NMDA‐Mediated Excitotoxicity: Evidence for Its Action as an NMDA Receptor Antagonist

Aurintricarboxylic Acid Prevents NMDA‐Mediated Excitotoxicity: Evidence for Its Action as an NMDA Receptor Antagonist

Mimicry of Biological Macromolecules by Polyaromatic Anionic Compounds

Alteration of Intrinsic Biological Rhythms during Interferon Treatment and Its Possible Mechanism

Contact Info

Product

Resources

About