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dc.contributor.authorAsico, L.D.
dc.contributor.authorBeitelshees, A.L.
dc.contributor.authorFeranil, J.B.
dc.contributor.authorWang, X.
dc.contributor.authorJones, J.E.
dc.contributor.authorArmando, I.
dc.contributor.authorCuevas, S.G.
dc.contributor.authorJose, P.A.
dc.contributor.authorVillar, V.A.M.
dc.date.accessioned2020-04-27T19:48:55Z
dc.date.available2020-04-27T19:48:55Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85083438370&doi=10.1096%2ffj.201902448R&partnerID=40&md5=7530b33510198e2b38167577ba54468b
dc.identifier.urihttp://hdl.handle.net/10713/12656
dc.description.abstractAcute renal depletion of sorting nexin 1 (SNX1) in mice results in blunted natriuretic response and hypertension due to impaired dopamine D5 receptor (D5R) activity. We elucidated the molecular mechanisms for these phenotypes in Snx1−/− mice. These mice had increased renal expressions of angiotensin II type 1 receptor (AT1R), NADPH oxidase (NOX) subunits, D5R, and NaCl cotransporter. Basal reactive oxygen species (ROS), NOX activity, and blood pressure (BP) were also higher in Snx1-/- mice, which were normalized by apocynin, a drug that prevents NOX assembly. Renal proximal tubule (RPT) cells from hypertensive (HT) Euro-American males had deficient SNX1 activity, impaired D5R endocytosis, and increased ROS compared with cells from normotensive (NT) Euro-American males. siRNA-mediated depletion of SNX1 in RPT cells from NT subjects led to a blunting of D5R agonist-induced increase in cAMP production and decrease in Na+ transport, effects that were normalized by over-expression of SNX1. Among HT African-Americans, three of the 12 single nucleotide polymorphisms interrogated for the SNX1 gene were associated with a decrease in systolic BP in response to hydrochlorothiazide (HCTZ). The results illustrate a new paradigm for the development of hypertension and imply that the trafficking protein SNX1 may be a crucial determinant for hypertension and response to antihypertensive therapy.en_US
dc.description.urihttps://doi.org/10.1096/fj.201902448Ren_US
dc.language.isoen_USen_US
dc.publisherJohn Wiley and Sons Inc.en_US
dc.relation.ispartofFASEB Journal
dc.subjectdopamine D5 receptoren_US
dc.subjecthypertensionen_US
dc.subjectoxidative stressen_US
dc.subjectrenal proximal tubule cellsen_US
dc.subjectsorting nexin 1en_US
dc.titleSorting nexin 1 loss results in increased oxidative stress and hypertensionen_US
dc.typeArticleen_US
dc.identifier.doi10.1096/fj.201902448R
dc.identifier.pmid32293069


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