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Chemical Compound Review

Pandavir     (2R)-2-[(2R,3S,6R)-6- [[(2S,4R,5R,7S,9R...

Synonyms: nigericin, Polyetherin A, Azalomycin A, Azalomycin M, Helixin A, ...
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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


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


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].


  1. Enhancement of the cytotoxic effect of anti-carcinoembryonic antigen immunotoxins by adenovirus and carboxylic ionophores. Griffin, T.W., Childs, L.R., FitzGerald, D.J., Levin, L.V. J. Natl. Cancer Inst. (1987) [Pubmed]
  2. Modulation of glycosylation and transport of viral membrane glycoproteins by a sodium ionophore. Alonso-Caplen, F.V., Compans, R.W. J. Cell Biol. (1983) [Pubmed]
  3. K+/H+-antiporter nigericin arrests DNA synthesis in Ehrlich ascites carcinoma cells. Margolis, L.B., Novikova I, Y., Rozovskaya, I.A., Skulachev, V.P. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  4. Enhancement of cytotoxicities of ricin and Pseudomonas toxin in Chinese hamster ovary cells by nigericin. Ray, B., Wu, H.C. Mol. Cell. Biol. (1981) [Pubmed]
  5. Acid pH in tumors and its potential for therapeutic exploitation. Tannock, I.F., Rotin, D. Cancer Res. (1989) [Pubmed]
  6. Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Farrens, D.L., Altenbach, C., Yang, K., Hubbell, W.L., Khorana, H.G. Science (1996) [Pubmed]
  7. Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1/mBBP. Selenko, P., Gregorovic, G., Sprangers, R., Stier, G., Rhani, Z., Krämer, A., Sattler, M. Mol. Cell (2003) [Pubmed]
  8. A potassium ionophore (Nigericin) inhibits stimulation of human lymphocytes by mitogens. Daniele, R.P., Holian, S.K., Nowell, P.C. J. Exp. Med. (1978) [Pubmed]
  9. Oxalate transport by anion exchange across rabbit ileal brush border. Knickelbein, R.G., Aronson, P.S., Dobbins, J.W. J. Clin. Invest. (1986) [Pubmed]
  10. The influence of calcium and reactive oxygen species on influenza virus-induced apoptosis. Olsen, C.W., Dybdahl-Sissoko, N., Hinshaw, V.S. Cell Death Differ. (1996) [Pubmed]
  11. Rapid intracellular acidification and cell death by H2O2 and alloxan in pancreatic beta cells. Nakamura, U., Iwase, M., Uchizono, Y., Sonoki, K., Sasaki, N., Imoto, H., Goto, D., Iida, M. Free Radic. Biol. Med. (2006) [Pubmed]
  12. The use of valinomycin, nigericin and trichlorocarbanilide in control of the protonmotive force in Escherichia coli cells. Ahmed, S., Booth, I.R. Biochem. J. (1983) [Pubmed]
  13. Effect of N, N'-dicyclohexylcarbodiimide and nigericin on Staphylococcus aureus susceptibility to gentamicin. Mandel, L.J., Eisenberg, E.S., Simkin, N.J., Miller, M.H. Antimicrob. Agents Chemother. (1983) [Pubmed]
  14. Relations between intracellular ions and energy metabolism under acidotic conditions: a study with nigericin in synaptosomes, neurons, and C6 glioma cells. Erecińska, M., Nelson, D., Dagani, F., Deas, J., Silver, I.A. J. Neurochem. (1993) [Pubmed]
  15. Active transport of calcium in Neurospora plasma membrane vesicles. Stroobant, P., Scarborough, G.A. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  16. Conformation and orientation of a protein folding intermediate trapped by adsorption. Engel, M.F., Visser, A.J., van Mierlo, C.P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  17. The acid deoxyribonuclease of neutrophils: a possible participant in apoptosis-associated genome destruction. Gottlieb, R.A., Giesing, H.A., Engler, R.L., Babior, B.M. Blood (1995) [Pubmed]
  18. Interdependent regulation of intracellular acidification and SHP-1 in apoptosis. Thangaraju, M., Sharma, K., Liu, D., Shen, S.H., Srikant, C.B. Cancer Res. (1999) [Pubmed]
  19. Potassium ion influx and Na+,K+-ATPase activity are required for the hamster sperm acrosome reaction. Mrsny, R.J., Meizel, S. J. Cell Biol. (1981) [Pubmed]
  20. Endocytic vesicles from renal papilla which retrieve the vasopressin-sensitive water channel do not contain a functional H+ ATPase. Lencer, W.I., Verkman, A.S., Arnaout, M.A., Ausiello, D.A., Brown, D. J. Cell Biol. (1990) [Pubmed]
  21. Intracellular pH regulation during spreading of human neutrophils. Demaurex, N., Downey, G.P., Waddell, T.K., Grinstein, S. J. Cell Biol. (1996) [Pubmed]
  22. NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors. Gerasimenko, J.V., Maruyama, Y., Yano, K., Dolman, N.J., Tepikin, A.V., Petersen, O.H., Gerasimenko, O.V. J. Cell Biol. (2003) [Pubmed]
  23. Chloroplast phosphoproteins: regulation of excitation energy transfer by phosphorylation of thylakoid membrane polypeptides. Bennett, J., Steinback, K.E., Arntzen, C.J. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  24. Cyclic AMP functions as a primary sexual signal in gametes of Chlamydomonas reinhardtii. Pasquale, S.M., Goodenough, U.W. J. Cell Biol. (1987) [Pubmed]
  25. The electrochemical gradient of protons and its relationship to active transport in Escherichia coli membrane vesicles. Ramos, S., Schuldiner, S., Kaback, H.R. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  26. pH homeostasis in Leishmania donovani amastigotes and promastigotes. Glaser, T.A., Baatz, J.E., Kreishman, G.P., Mukkada, A.J. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  27. Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction. Schuel, H., Goldstein, E., Mechoulam, R., Zimmerman, A.M., Zimmerman, S. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  28. Membrane potential and gentamicin uptake in Staphylococcus aureus. Mates, S.M., Eisenberg, E.S., Mandel, L.J., Patel, L., Kaback, H.R., Miller, M.H. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  29. Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp. DSM4137. Harvey, B.M., Mironenko, T., Sun, Y., Hong, H., Deng, Z., Leadlay, P.F., Weissman, K.J., Haydock, S.F. Chem. Biol. (2007) [Pubmed]
  30. 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. Vandenbroeck, K., Alloza, I., Brehmer, D., Billiau, A., Proost, P., McFerran, N., Rüdiger, S., Walker, B. J. Biol. Chem. (2002) [Pubmed]
  31. A family of yeast proteins mediating bidirectional vacuolar amino acid transport. Russnak, R., Konczal, D., McIntire, S.L. J. Biol. Chem. (2001) [Pubmed]
  32. An inhibitory switch derepressed by pbx, hox, and Meis/Prep1 partners regulates DNA-binding by pbx1 and E2a-pbx1 and is dispensable for myeloid immortalization by E2a-pbx1. Calvo, K.R., Knoepfler, P., McGrath, S., Kamps, M.P. Oncogene (1999) [Pubmed]
  33. A screen for nigericin-resistant yeast mutants revealed genes controlling mitochondrial volume and mitochondrial cation homeostasis. Kucejova, B., Kucej, M., Petrezselyova, S., Abelovska, L., Tomaska, L. Genetics (2005) [Pubmed]
  34. Glutamic acid-113 serves as the retinylidene Schiff base counterion in bovine rhodopsin. Sakmar, T.P., Franke, R.R., Khorana, H.G. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  35. Hydrogen ion-mediated enhancement of cytotoxicity of bis-chloroethylating drugs in rat mammary carcinoma cells in vitro. Jähde, E., Glüsenkamp, K.H., Klünder, I., Hülser, D.F., Tietze, L.F., Rajewsky, M.F. Cancer Res. (1989) [Pubmed]
  36. Enhancement of photodynamic cell killing (with chloroaluminum phthalocyanine) by treatment of V79 cells with the ionophore nigericin. Varnes, M.E., Clay, M.E., Freeman, K., Antunez, A.R., Oleinick, N.L. Cancer Res. (1990) [Pubmed]
  37. The amiloride-sensitive Na+/H+ antiport in 3T3 fibroblasts. Frelin, C., Vigne, P., Lazdunski, M. J. Biol. Chem. (1983) [Pubmed]
  38. Thapsigargin causes Ca2+ release and collapse of the membrane potential of Trypanosoma brucei mitochondria in situ and of isolated rat liver mitochondria. Vercesi, A.E., Moreno, S.N., Bernardes, C.F., Meinicke, A.R., Fernandes, E.C., Docampo, R. J. Biol. Chem. (1993) [Pubmed]
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