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Ceramide Mediates Acute Oxygen Sensing in Vascular Tissues

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Ceramide Mediates Acute Oxygen Sensing in Vascular Tissues

dc.contributor.author	Moreno, Laura	es_ES
dc.contributor.author	Moral-Sanz, Javier	es_ES
dc.contributor.author	Morales-Cano, Daniel	es_ES
dc.contributor.author	Barreira, Bianca	es_ES
dc.contributor.author	Moreno, Enrique	es_ES
dc.contributor.author	Ferrarini, Alessia	es_ES
dc.contributor.author	Pandolfi, Rachele	es_ES
dc.contributor.author	Ruperez, Francisco J.	es_ES
dc.contributor.author	Cortijo Gimeno, Julio	es_ES
dc.contributor.author	Sanchez-Luna, Manuel	es_ES
dc.contributor.author	Villamor, Eduardo	es_ES
dc.contributor.author	Perez-Vizcaino, Francisco	es_ES
dc.contributor.author	Cogolludo, Angel	es_ES
dc.date.accessioned	2015-06-10T09:45:37Z
dc.date.available	2015-06-10T09:45:37Z
dc.date.issued	2014	es_ES
dc.identifier.citation	Antioxidants & Redox Signaling Vol. 20 Issue 1: pp. 1-14	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44287
dc.description.abstract	AbstractAims: A variety of vessels, such as resistance pulmonary arteries (PA) and fetoplacental arteries and the ductus arteriosus (DA) are specialized in sensing and responding to changes in oxygen tension. Despite opposite stimuli, normoxic DA contraction and hypoxic fetoplacental and PA vasoconstriction share some mechanistic features. Activation of neutral sphingomyelinase (nSMase) and subsequent ceramide production has been involved in hypoxic pulmonary vasoconstriction (HPV). Herein we aimed to study the possible role of nSMase-derived ceramide as a common factor in the acute oxygen-sensing function of specialized vascular tissues. Results: The nSMase inhibitor GW4869 and an anticeramide antibody reduced the hypoxic vasoconstriction in chicken PA and chorioallantoic arteries (CA) and the normoxic contraction of chicken DA. Incubation with interference RNA targeted to SMPD3 also inhibited HPV. Moreover, ceramide and reactive oxygen species production were increased by hypoxia in PA and by normoxia in DA. Either bacterial sphingomyelinase or ceramide mimicked the contractile responses of hypoxia in PA and CA and those of normoxia in the DA. Furthermore, ceramide inhibited voltage-gated potassium currents present in smooth muscle cells from PA and DA. Finally, the role of nSMase in acute oxygen sensing was also observed in human PA and DA. Innovation: These data provide evidence for the proposal that nSMase-derived ceramide is a critical player in acute oxygen-sensing in specialized vascular tissues. Conclusion: Our results indicate that an increase in ceramide generation is involved in the vasoconstrictor responses induced by two opposite stimuli, such as hypoxia (in PA and CA) and normoxia (in DA). Antioxid. Redox Signal. 20, 1–14.	es_ES
dc.title	Ceramide Mediates Acute Oxygen Sensing in Vascular Tissues	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.1089/ars.2012.4752	es_ES
dc.identifier.idgrec	100085	es_ES