2015
DOI: 10.1159/000430395
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Spongionella Secondary Metabolites Regulate Store Operated Calcium Entry Modulating Mitochondrial Functioning in SH-SY5Y Neuroblastoma Cells

Abstract: Background/Aims: The effect of four secondary metabolites isolated from sponge Spongionella, gracilins H, A, L and tetrahydroaplysulphurin-1 on Calcium ion (Ca2+) fluxes were studied in SH-SY5Y neuroblastoma cells. Methods and Results: These compounds did not modify cytosolic baseline Ca2+-levels. Nevertheless, when cytosolic Ca2+-influx through store operated calcium channels (SOC channels) was stimulated with Thapsigargin (Tg), a strong inhibition was observed in the presence… Show more

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Cited by 16 publications
(27 citation statements)
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“…The mode of action of these compounds was assessed using a scaled-down version of Egan's bhematin assay demonstrating that marine isonitriles inhibit b-hematin crystallisation and supported by ab initio calculations of the stability of the isonitrile complexes bound to iron in heme. 700 Gracilins A, H and L 701,702 along with tetrahydroaplysulphurin-1, 703 all isolated from Spongionella sp., were found to modulate mitochondrial function in neuroblastoma cells by regulating storage of calcium entry in a similar manner to cyclosporine A via binding to cyclophilin D. 704 Okadaic acid (OA), a potent marine cytotoxin that inhibits protein phosphatases, was originally isolated from Halichondria okadai but later identied as being produced by the dinoagellate Prorocentrum lima and actively bioaccumulated by the sponge. 705 The role and mechanism of OA accumulation by Halichondria has not yet been established.…”
Section: Spongesmentioning
confidence: 99%
“…The mode of action of these compounds was assessed using a scaled-down version of Egan's bhematin assay demonstrating that marine isonitriles inhibit b-hematin crystallisation and supported by ab initio calculations of the stability of the isonitrile complexes bound to iron in heme. 700 Gracilins A, H and L 701,702 along with tetrahydroaplysulphurin-1, 703 all isolated from Spongionella sp., were found to modulate mitochondrial function in neuroblastoma cells by regulating storage of calcium entry in a similar manner to cyclosporine A via binding to cyclophilin D. 704 Okadaic acid (OA), a potent marine cytotoxin that inhibits protein phosphatases, was originally isolated from Halichondria okadai but later identied as being produced by the dinoagellate Prorocentrum lima and actively bioaccumulated by the sponge. 705 The role and mechanism of OA accumulation by Halichondria has not yet been established.…”
Section: Spongesmentioning
confidence: 99%
“…These compounds have shown interesting antioxidant effects and the inhibition of Alzheimer hallmarks ( 19 , 20 ). In addition, Gracilin H, A, L, and Tetrahydroaplysulphurin-1 were able to form complexes with intracellular Cyps ( 21 ). In the case of Cyp A, Spongionella compounds showed a K D in the micromolar range, similar to CsA, a well-known Cyp A binder, and in the same way, they regulated transcriptional factors and the production of interleukin 2 (IL-2) ( 21 , 22 ).…”
Section: Introductionmentioning
confidence: 99%
“…In addition, Gracilin H, A, L, and Tetrahydroaplysulphurin-1 were able to form complexes with intracellular Cyps ( 21 ). In the case of Cyp A, Spongionella compounds showed a K D in the micromolar range, similar to CsA, a well-known Cyp A binder, and in the same way, they regulated transcriptional factors and the production of interleukin 2 (IL-2) ( 21 , 22 ). Thus, these compounds could mimic other CsA effects related to the immune response.…”
Section: Introductionmentioning
confidence: 99%
“…Also consolidated in Table 3 is the pharmacological activity (IC 50 for enzyme or receptor inhibition) of marine-derived compounds , but the mechanism of action remained undetermined at the time of publication: a dinoflagellate Dinophysis acuminate new polyether macrolide acuminolide A (253) [272]; fungus Alternaria alternata alternariol derivatives (255)(256)(257)…”
Section: Marine Compounds With Miscellaneous Mechanisms Of Actionmentioning
confidence: 99%