Genistein effects on Ca2+ handling in human umbilical artery: inhibition of sarcoplasmic reticulum Ca2+ release and of voltage-operated Ca2+ channels

Isoflavones are a group of natural phytoestrogens including the compound genistein. Health beneficial effects have been attributed to the consumption of this compound, but the fact that it has estrogen-like activity has raised doubts regarding its potential risk in infants, newborns, or in the fetus and placenta during pregnancy. This work is aimed at studying genistein effects on Ca2+ handling by smooth muscle cells of the human umbilical artery (HUA). Using fluorometric techniques, we found that in these cells genistein reduces the intracellular Ca2+ peak produced by serotonin. The same result could be demonstrated in absence of extracellular Ca2+, suggesting that the isoflavone reduces Ca2+ release from the sarcoplasmic reticulum. Force measurement experiments strengthen these results, since genistein reduced the peak force attained by intact HUA rings stimulated by serotonin in a Ca2+-free solution. Moreover, genistein induced the relaxation of HUA rings precontracted either with serotonin or a depolarizing high-extracellular K+ solution, hinting at a reduction of extracellular Ca2+ entry to the cell. This was confirmed by whole-cell patch-clamp experiments where it was shown that the isoflavone inhibits ionic currents through voltage-operated Ca2+ channels. In summary, we show that genistein inhibits two mechanisms that could increase intracellular Ca2+ in human umbilical smooth muscle cells, behaving in this way as a potential vasorelaxing substance of fetal vessels. Taking into account that genistein is able to cross the placental barrier, these data show that isoflavones may have important implications in the regulation of feto-maternal blood flow in pregnant women who consume soy-derived products as part of their meals.ResumenLas isoflavonas son un grupo de fitoestrógenos naturales que incluyen la genisteína. Al consumo de este compuesto se le han atribuido efectos beneficiosos para la salud, pero su actividad similar a los estrógenos permite pensar en efectos indeseados en niños o en el feto o la placenta durante el embarazo. En este trabajo se estudian los efectos de la genisteína sobre el manejo de Ca2+ por las células de músculo liso de la arteria umbilical humana (AUH). Mediante la utilización de técnicas fluorométricas se observó que la genisteína reduce el pico de Ca2+ intracelular producido por la serotonina en estas células incluso en ausencia de Ca2+ extracelular, lo que sugiere que la isoflavona reduce la liberación de Ca2+ a partir del retículo sarcoplásmico. Los experimentos de medida de fuerza refuerzan estos resultados, ya que la genisteína redujo la fuerza pico desarrollada por serotonina en anillos intactos de AUH en una solución libre de Ca2+. Además, la genisteína indujo la relajación de anillos de AUH precontraídos con serotonina o con una solución despolarizante de alto K+ extracelular, lo que apunta a una reducción de la entrada de Ca2+ desde el exterior de la célula. Con la técnica de “patch-clamp” en configuración de célula entera, los resultados confirmaron que la isoflavona inhibe corrientes iónicas a través de canales de Ca2+ operados por el voltaje. En resumen, mostramos que la genisteína inhibe dos mecanismos que incrementan el Ca2+ intracelular en células de músculo liso de AUH, comportándose de esta manera como un potencial vasorrelajante de los vasos fetales. Dado que la genisteína atraviesa la barrera placentaria, estos datos muestran que las isoflavonas podrían tener consecuencias en la regulación del flujo materno-fetal en mujeres embarazadas que incluyan productos derivados de la soja como parte de sus dietas.

• Publication year

  2009

• Venue

  Journal of physiology and biochemistry

• Publication date

  2009-06-01

• Fields of study

  Not labeled

• Identifiers
  DOI 10.1007/BF03179062PMID 19886390
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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