Gossypol stimulates opening of a Ca2+ - and Na+ -permeable but Ni2+ - and Co2+ -impermeable pore in bEND.3 endothelial cells

Clinical and Experimental Pharmacology & Physiology
Cing-Yu ChenShu-Er Yang

Abstract

Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti-cancer properties and has recently shown some success in the treatment of glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca2+ concentration ([Ca2+ ]i ) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3 hour and 18 hour exposures, 10 µmol/L gossypol caused 23% and 65% cell death, respectively; 3 µmol/L gossypol caused no and 21% cell death, respectively. [Ca2+ ]i was raised concentration-dependently by 1-10 µmol/L gossypol. We then explored the Ca2+ signalling triggered by 3 µmol/L gossypol, which inflicted minimal toxicity: the Ca2+ signal was composed largely of Ca2+ influx and to a small extent, intracellular Ca2+ release. Such Ca2+ influx was much larger than store-operated Ca2+ influx triggered by maximal Ca2+ pool depletion. The Ca2+ influx triggered by 3 and 10 µmol/L gossypol caused NO release and cell death, respectively. Gossypol also triggered influx of Mn2+ and Na+ , but not Ni2+ and Co2+ . Gossypol-triggered Ca2+ signal was inhibited only by 14% and 37% by 100 µmol/L La3+ and 10 µmol/L nimodipine, respectively; and...Continue Reading

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Citations

Jun 18, 2019·Fundamental & Clinical Pharmacology·King-Chuen WuLi-Yun Chang
Oct 31, 2020·Clinical and Experimental Pharmacology & Physiology·Nargiza M ChorievaRavshan Z Sabirov

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