Disease relevance of nigericin

• The effects of the UV radiation-inactivated human adenovirus and the carboxylic ionophores monensin and nigericin were examined on immunotoxin cytotoxicity to the human colorectal adenocarcinoma cell line LoVo [1].
• Nigericin, an ionophore that facilitates transport of potassium ions across membranes, blocked the replication of both influenza virus and VSV in MDCK cell monolayers, indicating that the ion specificity of ionophores influences their effect on the replication of enveloped viruses [2].
• K+/H+-antiporter nigericin arrests DNA synthesis in Ehrlich ascites carcinoma cells [3].
• These results suggest a common step in the intoxication process of ricin and Pseudomonas toxin, the rate of which is facilitated by pretreatment with nigericin [4].
• Ionophores such as nigericin or CCCP cause acid loading of cells in culture and are toxic only at low pHc; this toxicity is enhanced by agents such as amiloride or DIDS which impair mechanisms involved in regulation of pHi [5].

High impact information on nigericin

• Such changes in rhodopsin were explored by construction of double cysteine mutants, each containing one cysteine at the cytoplasmic end of helix C and one cysteine at various positions in the cytoplasmic end of helix F [6].
• The structure of the C-terminal RRM (RRM3) of human U2AF(65) complexed to an N-terminal peptide of SF1 reveals an extended negatively charged helix A and an additional helix C [7].
• Nigericin, an ionophore that exchanges K+ for H+ across most biologic membranes, reversibly inhibited the proliferative response of human lymphocytes to phytohemagglutinin (PHA) [8].
• A potassium ionophore (Nigericin) inhibits stimulation of human lymphocytes by mitogens [8].
• Addition of K+ and nigericin only slightly decreased the Cl gradient-stimulated oxalate uptake, which indicates that this stimulation was not primarily due to the Cl gradient generating an inside alkaline pH gradient via Cl:OH exchange [9].

Chemical compound and disease context of nigericin

• In terms of ROS, neither treatment with antioxidants, N(2) flushing to induce hypoxia, nor nigericin (a compound which, like bcl-2, stabilizes the mitochondrial membrane potential against the effects of ROS and subsequent Ca(2+) dysregulation) were able to block Ty/Ont-induced apoptosis [10].
• On the other hand, NIT-1 cells were resistant to alloxan toxicity, but treatment with alloxan and nigericin strikingly enhanced the cytotoxicity [11].
• Valinomycin, nigericin and trichlorocarbanilide were assessed for their ability to control the protonmotive force in Escherichia coli cells [12].
• Effect of N, N'-dicyclohexylcarbodiimide and nigericin on Staphylococcus aureus susceptibility to gentamicin [13].
• Effects of nigericin were investigated in rat brain synaptosomes, cultured neurons, and C6 glioma cells to characterize the relations among ATP synthesis, [Na+]i, [K+]i, and [Ca2+]i, and pH under conditions when [H+]i is substantially increased and transmembrane electrical potential is decreased [14].

Biological context of nigericin

• Energized Ca2+ uptake is stimulated by the permeant anion SCN- to a degree that varies reciprocally with the ability of this anion to dissipate the membrane potential, and is inhibited by K+ in the presence of nigericin [15].
• This side preferentially interacts with the interface and includes residues in helix C, the calcium binding site, and part of the beta-domain [16].
• Glucose and anaerobiosis potentiate the nigericin effect [3].
• DNA from neutrophils treated with nigericin in buffers of defined pH displayed nucleosomal ladders whose prominence varied with pH in a manner that paralleled the pH dependence of the plasmid cleavage assays, consistent with internucleosomal DNA cleavage by the acid endonuclease [17].
• Apoptosis could be induced by nigericin clamping of pHi to 6 [18].

Anatomical context of nigericin

• Neither nigericin added alone (0.9 mM K+) nor nigericin plus 12 mM K+ added to a low Ca2+ (0.35 mM) system resulted in acrosome reactions [19].
• Acidification of cortical endosomes was reversed with nigericin and strongly inhibited by N-ethyl-maleimide [20].
• Neutrophils spread normally when the oxidase was blocked or when pHi was clamped near physiological values with nigericin [21].
• The Ca2+ release was unaffected by procedures interfering with acidic organelles (bafilomycin, brefeldin, and nigericin) [22].
• Addition of ATP to isolated chloroplast thylakoid membranes at 20 degrees C results in a time-dependent reduction of chlorophyll fluorescence emission; this is blocked by diuron but not by nigericin [23].

Associations of nigericin with other chemical compounds

• No activation of mating events is induced by calcium plus ionophores, 8-bromo-cGMP, dibutyryl-cGMP, nigericin at alkaline pH, phorbol esters, or forskolin [24].
• In addition, deltapH and delta psi can be varied reciprocally in the presence of valinomycin and nigericin [25].
• Treatment with ionophores, such as nigericin and carbonyl cyanide m-chlorophenylhydrazone and the ATPase inhibitor dicyclohexylcarbodiimide, reduced pH gradients in both stages [26].
• Under conditions where anandamide completely blocks the egg jelly-stimulated acrosome reaction, it does not inhibit the acrosome reaction artificially initiated by ionomycin, which promotes Ca2+ influx, and nigericin, which activates K+ channels in sperm [27].
• Dramatically, when the ionophore nigericin is added at pH 5.0, gentamicin uptake is induced, there is a striking decrease in viability, and the effect is associated with an increase in delta psi at the expense of delta pH [28].
• In particular, we present evidence that in nigericin, nanchangmycin, and monensin, an unusual ketosynthase-like protein, KSX, transfers the initially formed linear polyketide chain to a discrete acyl carrier protein, ACPX, for oxidative cyclization [29].

Gene context of nigericin

• The conserved helix C region in the superfamily of interferon-gamma /interleukin-10-related cytokines corresponds to a high-affinity binding site for the HSP70 chaperone DnaK [30].
• Conserved DnaK-binding sites were identified in the N-terminal half of helix B and in the C-terminal half of helix C, both of which are located at the IFN-gamma dimer interface [30].
• Transport by AVT1 and AVT6 requires ATP for function and is abolished in the presence of nigericin, indicating that the same pH gradient can drive amino acid transport in opposing directions [31].
• While stabilizing the heterodimer, the 310 helix C-terminal to the Pbx1 HD was also dispensable for the ability of E2a-Pbx1 to heterodimerize with Hox proteins and immortalize myeloblasts [32].
• Direct examination of intact cells by electron microscopy indicated that mutants lacking MDM31 and/or MDM32 genes contain dramatically enlarged, spherical mitochondria and that these morphological abnormalities can be alleviated by nigericin [33].

Analytical, diagnostic and therapeutic context of nigericin

• By using site-directed mutagenesis, charged amino acids in bovine rhodopsin transmembrane helix C were systematically replaced [34].
• As indicated by experiments using the ionophor nigericin for rapid equilibration of pHe and intracellular pH (pHi; measured with pH-sensitive microelectrodes), modulation of drug action by varying pHe primarily resulted from the concomitant decrease in pHi [35].
• The K+/H+ ionophore nigericin dramatically increases killing of V79 cells by photodynamic therapy (PDT), when cells pretreated with 1 microM chloroaluminum phthalocyanine are incubated with nigericin before exposure to red light [36].
• However, after treatment of the cells with ammonia or nigericin, serum produces a 40-fold stimulation of the rate of the amiloride-sensitive 22Na+ uptake [37].
• In addition, we have found no evidence for an increase in intracellular Ca2+ by release of the ion from intracellular stores by nigericin, measuring changes in cytosolic Ca2+ by dual wavelength spectrofluorometry in fura-2-loaded T. brucei bloodstream trypomastigotes or measuring Ca2+ transport in digitonin-permeabilized cells [38].

References