Disease relevance of valinomycin

• The effect was not due to toxicity to the cells, nor appeared to be due to the effects of valinomycin as an uncoupler of oxidative phosphorylation [1].
• Recent studies have identified older, low-density sickle red blood cells (SSRBCs) that were resistant to dehydration by valinomycin, a K(+) ionophore [2].
• The effect of valinomycin on nontransformed 3T3 mouse and Rat-1 cells is nontoxic, whereas it acts with increasing toxicity on the transformed cells in the order 3T6 mouse, polyoma-3T3 mouse, temperature-sensitively Rous sarcoma virus-transformed Rat-1 at permissive temperature, and SV40-3T3 cells [3].
• Experiments with E. coli phospholipid liposomes revealed that HLz dissipated the valinomycin-induced transmembrane electrochemical potential, but WLz did not [4].
• We confirmed that in starved, valinomycin-treated cells of Streptococcus lactis 7962, Tl+ ions distributed themselves across the bacterial membrane in response to the potassium diffusion potential [5].

High impact information on valinomycin

• Enhancement of the electrical excitability of neuroblastoma cells by valinomycin [6].
• For comparison, intact liver cells were treated with valinomycin, a potassium ionophore, which gave rise to an atypical cell death, with chromatin condensation appearing without DNA fragmentation [7].
• When the membrane potential is approximated by the Nernst potential for K+, as in the presence of the K+ ionophore valinomycin, equilibrium thermodynamics predicts that the Na+-HCO3- cotransport system should come to equilibrium and mediate no net flux when (Na)i/(Na)o = [(HCO3)o/(HCO3)i]n[(K)o/(K)i]n-1, where n is the HCO3-:Na+ stoichiometry [8].
• No change in Na uptake pattern was observed with valinomycin, and initial Na uptake was not significantly different in normal versus uremic synaptosomes [9].
• This bicarbonate- and pH gradient-stimulated butyrate uptake was not inhibited by either voltage clamping, with equimolar intravesicular and extravesicular K+ and valinomycin, or 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an anion-exchange inhibitor [10].

Chemical compound and disease context of valinomycin

• Here we report that the incorporation of valinomycin into multilamellar liposomes composed of dimyristoyl phosphatidyl choline:cholesterol:phosphatidyl serine (10:4:1 M ratio) results in a profound reduction in toxicity with maintainence of antitumor efficacy [11].
• The use of valinomycin, nigericin and trichlorocarbanilide in control of the protonmotive force in Escherichia coli cells [12].
• DCCD was the best inhibitor of mycoplasma attachment, and in combination with valinomycin attachment, capacity decreased by about 40% [13].
• Entry of poliovirus into cells is blocked by valinomycin and concanamycin A [14].
• We have reevaluated the stoichiometry of Na+ and alpha-aminoisobutyric acid (alpha-AIB) cotransport in Ehrlich ascites tumor cells depleted of Na+ and ATP by incubation in Na+-free HEPES-buffered medium (pH 7.2) containing 160 mM K+ and 2.5 microM valinomycin [15].

Biological context of valinomycin

• PMN from patients with CGD had normal calculated resting membrane potentials and normal responses elicited by the potassium ionophore valinomycin [16].
• Valinomycin (1 nM) did not stimulate the AR when added together with K+ (3-24 mM) to sperm incubated in 0.9 mM K+ for 3.5 h but markedly decreased sperm motility [17].
• This pattern was not affected by valinomycin in potassium-based media, nor could variable stoichiometry be attributed to altered hydrolysis of the sugar phosphate substrate [18].
• The phosphorylation was inhibited by DCCD any by tetraphenylboron and valinomycin [19].
• The mechanistic stoichiometry of vectorial H+ ejection coupled to electron transport from added ferrocytochrome c to oxygen by the cytochrome oxidase (EC 1.9.3.1) of rat liver mitoplasts was determined from measurements of the initial rates of electron flow and H+ ejection in the presence of K+ (with valinomycin) [20].

Anatomical context of valinomycin

• Membrane potentials and resistances of giant mitochondria. Metabolic dependence and the effects of valinomycin [21].
• Agents examined in this study included staphylococcal alpha-toxin and gramicidin, both of which selectively permeabilize plasma membranes for monovalent ions, the ionophores nigericin and valinomycin, and the Na+/K+ ATPase inhibitor ouabain [22].
• Proteolytic maturation of preCCP also occurred in the presence of valinomycin, suggesting that the precursor may be completely or partially translocated across the outer mitochondrial membrane independent of a potential across the inner mitochondrial membrane [23].
• Human lymphocytes separated from peripheral blood on Hypaque-Ficoll gradients are uniformly depolarized by gramicidin and hyperpolarized by valinomycin [24].
• It was found that, provided the medium is K+-free, valinomycin induces maturation in full-grown, but not in medium-sized, oocytes [25].

Associations of valinomycin with other chemical compounds

• The inhibition of secretion by valinomycin/K+ was ameliorated by imposition of a pH gradient, the second component of the delta P, and selective depletion of delta pH by nigericin also blocked secretion [26].
• A combination of ionophores expected to dissipate the vesicular membrane potential (valinomycin plus monensin) also fully inhibited the translocation [27].
• Light-induced changes in surface potential followed the changes observed in the M412 intermediate of the photocycle of bacteriorhodopsin as a function of pH, temperature, and response to antibiotics beauvericin and valinomycin [28].
• Assays of the quenching of acridine orange fluorescence showed that addition of both ATP and valinomycin to K+-loaded proteoliposomes led to the formation of a pH gradient that was acidic inside [29].
• Nevertheless, some, if not all, of the Mdr1 made in yeast was properly folded and functional because it could be photoaffinity labeled specifically with 8-azido-ATP and because cells overexpressing Mdr1 displayed increased resistance towards valinomycin, an ionophore known to interact with Mdr1 in animal cells [30].
• 18F-FDG incorporation was significantly increased by 30 min of treatment with valinomycin and was still apparent after 3.5 h of incubation [31].

Gene context of valinomycin

• However, IFN-gamma production induced by a combination of IL-15 and IL-18 was somewhat less sensitive to valinomycin, suggesting a protective effect of the cytokine combination against valinomycin [32].
• Indeed, valinomycin inhibits P-gp with an IC(50) similar to cyclosporin A yet apparently does not affect CYP3A4 function, and emetine and nobiletin are also specific for interaction with P-gp [33].
• In the case of cyclosporin A, vinblastine or valinomycin, this up-shift was found to be concomitant with the near-complete suppression of labeling with other mAbs specific for Pgp epitopes overlapping with UIC2, while pre-treatment with verapamil or Tween 80 brings about a modest suppression [34].
• The stimulation of mitochondrial PPase activity by FCCP, but not by valinomycin and nigericin, was greatly enhanced by the presence of DTT [35].
• Yeast cells expressing P-gp were valinomycin resistant [36].

Analytical, diagnostic and therapeutic context of valinomycin

• Changes in nuclear K+ electrochemical activity and total nuclear K+ content in salivary glands of Chironomus tentans were measured with ion-selective microelectrodes based on valinomycin and with flameless atomic absorption spectrometry, respectively [37].
• The nonshrinking, valinomycin-resistant (val-res) fractions, first detected by flow cytometry of density-fractionated SS RBCs, constituted up to 60% of the lightest, reticulocyte-rich (R1) cell fraction, and progressively smaller portions of the slightly denser R2 cells and discocytes [38].
• The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively [39].
• In the presence of valinomycin and K+, the absorption spectrum of FCCP is significantly perturbed, and there is also a large induced circular dichroism signal [40].
• Subsequent addition of valinomycin or the calcium ionophore A23187 leads to further fusion as shown by electron microscopy, light microscopy, and additional absorbance increase [41].

References