Polygodial induces inositol phosphate turnover in human neuroblastoma SH-SY5Y cells.
The pungent sesquiterpenoid unsaturated dialdehydes polygodial and isovelleral, have previously been shown to increase the intracellular free calcium concentration [Ca2+]i in human neuroblastoma SH-SY5Y cells, partly by a release from intracellular Ca2+ stores, whereas the non-pungent compound epipolygodial, had no effect on the [Ca2+]i. In this study, we investigated the effect of isovelleral, polygodial and epipolygodial on inositol phosphate (IP) formation on the assumption that there might be a correlation between the release of intracellular Ca2+ and pungency of the compounds. It was found that polygodial induced IP mobilization in a concentration dependent way, whereas isovelleral had no effect on the IP formation in the SH-SY5Y cells. Phosphoinositide (PPI) turnover was activated by epipolygodial, but only at concentrations 40-fold higher than for polygodial, which emphasizes the importance of the correct stereometry in the dialdehyde configuration for the biological activity of polygodial. The polygodial-induced formation of IP1 was reduced by 71% under extracellular calcium-free conditions, which suggests feedback interactions between the IP formation and the increase in [Ca2+]i to account for a periodic activation of phospholipase C(PLC).
Forsby
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Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden. annaf@neurochem.su.se
Walum
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D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D005246:Feedback; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007425:Intracellular Membranes / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010946:Plants, Medicinal; D000081223:Polycyclic Sesquiterpenes; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D000081223:Polycyclic Sesquiterpenes; D018160:Receptors, Cytoplasmic and Nuclear; D012717:Sesquiterpenes; C089286:isovelleral; C034380:polygodial; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium