Author | dc.contributor.author | Murphy, Matthew | |
Author | dc.contributor.author | Qin, Xia | |
Author | dc.contributor.author | Kaul, Shashank | |
Author | dc.contributor.author | Barrientos, Genaro | |
Author | dc.contributor.author | Zou, Zhen | |
Author | dc.contributor.author | Mathias, Clinton | |
Author | dc.contributor.author | Thomas, David | |
Author | dc.contributor.author | Bose, Diptiman | |
Admission date | dc.date.accessioned | 2020-04-30T15:45:19Z | |
Available date | dc.date.available | 2020-04-30T15:45:19Z | |
Publication date | dc.date.issued | 2020 | |
Cita de ítem | dc.identifier.citation | European Journal of Pharmacology Vol. 875 No. de artículo: 173036 May 2020 | es_ES |
Identifier | dc.identifier.other | 10.1016/j.ejphar.2020.173036 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/174233 | |
Abstract | dc.description.abstract | Ellagic acid, a naturally occurring phenol found in a variety of fruits and nuts has been shown to possess antiinflammatory properties. However, the mechanism of action behind its anti-inflammatory action is unclear. Using human Jurkat T cells, our study examined the effects of ellagic acid (EA) on Ca2+ handling, in particular, store-operated Ca2+ entry (SOCE), a process critical to proper T cell function. We observed that the acute addition of EA-induced Ca2+ release with an EC50 of 63 mu M. The Ca2+ release was significantly attenuated by Xestospongin C, a known inhibitor of the Inositol 1,4,5-trisphosphate receptor (IP3R) channel and was unaffected by the phospholipase C (PLC) inhibitor, U73122. Furthermore, chronic incubation of Jurkat T cells with EA not only decreased the ATP-induced Ca2+ release but also diminished the SOCE-mediated Ca2+ influx in a dose-dependent manner. This inhibition was confirmed by reduced Mn2+ entry rates in the EA-treated cells. The ATP-induced Ca2+ entry was also attenuated in EA-treated HEK293 cells transiently transfected with SOCE channel Orai1-myc and ER-sensor stromal interaction molecule (STIM1) (HEKSTIM/Orai). Moreover, EA treatment interfered with the Orai1 and STIM1 coupling by disrupting STIM1 puncta formation in the HEKSTIM/Orai rar cells. We observed that EA treatment reduced cytokine secretion and nuclear factor of activated T-cell transcriptional activity in stimulated T cells. Hence, by inhibiting SOCE mediated Ca2+ influx, EA decreased downstream activation of pro-inflammatory mediators. These results suggest a novel target for EA-mediated effects and provide insight into the mechanisms underlying EA-mediated anti-inflammatory effects. | es_ES |
Lenguage | dc.language.iso | en | es_ES |
Publisher | dc.publisher | Elsevier | es_ES |
Source | dc.source | European Journal of Pharmacology | es_ES |
Keywords | dc.subject | Ellagic acid | es_ES |
Keywords | dc.subject | Store-operated calcium entry (SOCE) | es_ES |
Keywords | dc.subject | Stromal interaction molecule (STIM) | es_ES |
Keywords | dc.subject | Orai | es_ES |
Keywords | dc.subject | Anti-inflammatory | es_ES |
Título | dc.title | The polyphenol ellagic acid exerts anti-inflammatory actions via disruption of store-operated calcium entry (SOCE) pathway activators and coupling mediators | es_ES |
Document type | dc.type | Artículo de revista | es_ES |
dcterms.accessRights | dcterms.accessRights | Acceso a solo metadatos | es_ES |
Cataloguer | uchile.catalogador | rvh | es_ES |
Indexation | uchile.index | Artículo de publicación ISI | |
Indexation | uchile.index | Artículo de publicación SCOPUS | |