Nigericin sodium salt

Nigericin sodium salt is an ionophore that exchanges K+ for H+ across biological membranes.

Ionophore is a lipid-soluble molecule that transports ions across the cell membrane.

In medium with Na+, nigericin scarcely affected ADP-induced platelets aggregation, and slightly inhibited thrombin-induced platelets aggregation. Also, nigericin decreased the cytoplasmic pH in the medium with Na+. The effects of nigericin on platelet aggregation are mainly due to its effects on the cytoplasmic pH [1]. The K+ ionophore nigericin is highly effective as an ionophore for Pb2+. Physiological concentrations of Ca2+ or Mg2+ didn’t inhibit nigericin-catalyzed Pb2+ transport, while K+ and Na+ concentrations (0-100 mM) modestly affected Pb2+ transport. Nigericin may be helpful in the treatment of Pb intoxication [2]. At two concentrations representing the low (5uM) and high ATP (1.5mM) ranges, Nigericin inhibited the ATP-driven transhydrogenase reaction at both ranges with a more pronounced effect on the low ATP concentration. At a concentration of 2.5 mM ATP, nigericin tripled the Oxonol response [3].

References:
[1].  Kitagawa S, Awai M, Kametani F. Relationship of the effects of nigericin on the aggregation and cytoplasmic pH of bovine platelets in the presence of different cations. Biochim Biophys Acta, 1987, 930(1): 48-54.
[2].  Hamidinia SA, Tan B, Erdahl WL, et al. The ionophore nigericin transports Pb2+ with high activity and selectivity: a comparison to monensin and ionomycin. Biochemistry, 2004, 43(50): 15956-15965.
[3].  Eytan GD, Carlenor E, Rydstr?m J. Energy-linked transhydrogenase. Effects of valinomycin and nigericin on the ATP-driven transhydrogenase reaction catalyzed by reconstituted transhydrogenase-ATPase vesicles. J Biol Chem, 1990, 265(22): 12949-12954.

Nigericin and grisorixin methyl ester from the Algerian soil-living Streptomyces youssoufiensis SF10 strain: a computational study on their epimeric structures and evaluation of glioblastoma stem cells growth inhibition.[Pubmed:29513090]

Nat Prod Res. 2019 Jan;33(2):266-273.

The present work describes the metabolites produced by a strain identified as Streptomyces youssoufiensis, whose secondary metabolites profile has not been studied so far. The crude ethyl acetate extract was analyzed by high performance liquid chromatography-electrospray ionization mass spectrometry, leading to the detection of the ionophoric polyethers nigericin, epinigericin, abierixin and the newly isolated grisorixin methyl ester. The presence of epimeric forms of nigericin/epinigericin and grisorixin/epigrisorixin has spurred density functional theory computational calculations. This analysis was able to provide the relative stability of the most favored epimers, setting the basis for general structural considerations applicable to several other polyethers. Both Nigericin sodium salt and grisorixin methyl ester showed to affect glioblastoma stem cells proliferation in a dose-dependent manner, with a higher activity for the more lipophilic grisorixin methyl ester (GI50 values of 3.85 and 3.05 muM for VIPI and COMI human glioblastoma stem cells, respectively).

[Isolation and structural elucidation of secondary metabolites from marine Streptomyces sp. SCSIO 1934].[Pubmed:22032140]

Zhongguo Zhong Yao Za Zhi. 2011 Jul;36(13):1763-8.

Marine Actinobacteria are emerging as new resources for bioactive natural products with promise in novel drug discovery. In recent years, the richness and diversity of marine Actinobacteria from the South China Sea and their ability in producing bioactive products have been investigated. The objective of this work is to isolate and identify bioactive secondary metabolites from a marine actinobacterium SCSIO 1934 derived from sediments of South China Sea. The strain was identified as a Streptomyces spieces by analyzing its 16S rDNA sequence. Streptomyces sp. SCSIO 1934 was fermented under optimized conditions and seven bioactive secondary metabolites were isolated and purified by chromatographic methods including colum chromatography over silica gel and Sephadex LH-20. Their structures were elucidated as 17-O-demethylgeldanamycin (1), lebstatin (2), 17-O-demethyllebstatin (3), nigericin (4), Nigericin sodium salt (5), abierixin (6), respectively, by detailed NMR spectroscopic data (1H, 13C, COSY, HSQC and HMBC). This work provided a new marine actinobacterium Streptomyces sp. SCSIO 1934, capable of producing diverse bioactive natural products.

Nigericin sodium salt is an antibiotic from Streptomyces hygroscopicus that works by acting as an H+, K+, and Pb2+ ionophore, a NLRP3 activator.

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