Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis

Abstract Our research introduces the natural flavonoid naringenin as a novel inhibitor of an emerging class of intracellular channels, Two-Pore Channel 2 (TPC2), as shown by electrophysiological evidence in a heterologous system, i.e. Arabidopsis vacuoles lacking endogenous TPCs. In view of the cont...

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Autores principales:	Irene Pafumi, Margherita Festa, Francesca Papacci, Laura Lagostena, Cristina Giunta, Vijay Gutla, Laura Cornara, Annarita Favia, Fioretta Palombi, Franco Gambale, Antonio Filippini, Armando Carpaneto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2396b1e6f3c34cb0bd9c8bcaaba6c66c
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spelling	oai:doaj.org-article:2396b1e6f3c34cb0bd9c8bcaaba6c66c2021-12-02T12:32:37ZNaringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis10.1038/s41598-017-04974-12045-2322https://doaj.org/article/2396b1e6f3c34cb0bd9c8bcaaba6c66c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04974-1https://doaj.org/toc/2045-2322Abstract Our research introduces the natural flavonoid naringenin as a novel inhibitor of an emerging class of intracellular channels, Two-Pore Channel 2 (TPC2), as shown by electrophysiological evidence in a heterologous system, i.e. Arabidopsis vacuoles lacking endogenous TPCs. In view of the control exerted by TPC2 on intracellular calcium signaling, we demonstrated that naringenin dampens intracellular calcium responses of human endothelial cells stimulated with VEGF, histamine or NAADP-AM, but not with ATP or Angiopoietin-1 (negative controls). The ability of naringenin to impair TPC2-dependent biological activities was further explored in an established in vivo model, in which VEGF-containing matrigel plugs implanted in mice failed to be vascularized in the presence of naringenin. Overall, the present data suggest that naringenin inhibition of TPC2 activity and the observed inhibition of angiogenic response to VEGF are linked by impaired intracellular calcium signaling. TPC2 inhibition is emerging as a key therapeutic step in a range of important pathological conditions including the progression and metastatic potential of melanoma, Parkinson’s disease, and Ebola virus infection. The identification of naringenin as an inhibitor of TPC2-mediated signaling provides a novel and potentially relevant tool for the advancement of this field of research.Irene PafumiMargherita FestaFrancesca PapacciLaura LagostenaCristina GiuntaVijay GutlaLaura CornaraAnnarita FaviaFioretta PalombiFranco GambaleAntonio FilippiniArmando CarpanetoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irene Pafumi Margherita Festa Francesca Papacci Laura Lagostena Cristina Giunta Vijay Gutla Laura Cornara Annarita Favia Fioretta Palombi Franco Gambale Antonio Filippini Armando Carpaneto Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis
description	Abstract Our research introduces the natural flavonoid naringenin as a novel inhibitor of an emerging class of intracellular channels, Two-Pore Channel 2 (TPC2), as shown by electrophysiological evidence in a heterologous system, i.e. Arabidopsis vacuoles lacking endogenous TPCs. In view of the control exerted by TPC2 on intracellular calcium signaling, we demonstrated that naringenin dampens intracellular calcium responses of human endothelial cells stimulated with VEGF, histamine or NAADP-AM, but not with ATP or Angiopoietin-1 (negative controls). The ability of naringenin to impair TPC2-dependent biological activities was further explored in an established in vivo model, in which VEGF-containing matrigel plugs implanted in mice failed to be vascularized in the presence of naringenin. Overall, the present data suggest that naringenin inhibition of TPC2 activity and the observed inhibition of angiogenic response to VEGF are linked by impaired intracellular calcium signaling. TPC2 inhibition is emerging as a key therapeutic step in a range of important pathological conditions including the progression and metastatic potential of melanoma, Parkinson’s disease, and Ebola virus infection. The identification of naringenin as an inhibitor of TPC2-mediated signaling provides a novel and potentially relevant tool for the advancement of this field of research.
format	article
author	Irene Pafumi Margherita Festa Francesca Papacci Laura Lagostena Cristina Giunta Vijay Gutla Laura Cornara Annarita Favia Fioretta Palombi Franco Gambale Antonio Filippini Armando Carpaneto
author_facet	Irene Pafumi Margherita Festa Francesca Papacci Laura Lagostena Cristina Giunta Vijay Gutla Laura Cornara Annarita Favia Fioretta Palombi Franco Gambale Antonio Filippini Armando Carpaneto
author_sort	Irene Pafumi
title	Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis
title_short	Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis
title_full	Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis
title_fullStr	Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis
title_full_unstemmed	Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis
title_sort	naringenin impairs two-pore channel 2 activity and inhibits vegf-induced angiogenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2396b1e6f3c34cb0bd9c8bcaaba6c66c
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Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis

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