Matches in SemOpenAlex for { <https://semopenalex.org/work/W4319007864> ?p ?o ?g. }
Showing items 1 to 74 of
74
with 100 items per page.
- W4319007864 abstract "Introduction: Cytochrome b5 reductase 3 (Cyb5R3) is a heme iron reductase that reverses oxidized soluble guanylate cyclase (sGC) heme iron (Fe 3+ Fe 2+ ) to preserve nitric oxide signaling. Under oxidative stress, such as occurs with sickle cell disease (SCD) and ischemic stroke, Cyb5R3 redox signaling provides resilience against tissue damage. A loss-of-function (roughly 50%) Cyb5R3 missense variant (T117S) occurs with high frequency (0.23 minor allele) in persons of African ancestry, who also suffer a greater burden of sickle cell anemia and ischemic stroke than other races. We hypothesized that Cyb5R3 regulates the erythropoietin response to ischemic stroke in a mouse model of SCD. Methods: Age-matched male SCD mice with wild-type Cyb5R3 (SS WT ) or T117S Cyb5R3 (SS T117S ) underwent middle cerebral artery occlusion (55 min) and reperfusion (48 hr). Blood was sampled at baseline and 48h reperfusion for hematology measurements. Brains were stained with 2,3,5-triphenyltetrazolium chloride to quantify infarct volume. Erythropoietin (EPO), heme oxygenase 1 (HMOX1) and sGC were assayed by Western blot. Results: We found brain infarct volume to be greater in SS T117S vs SS WT (63 vs 27 cm 3 , respectively; P=0.003). Red cells, hematocrit and hemoglobin decreased in SS T117S post-stroke, which was opposite to SS WT (red cells: -13% vs 13%, P=0.01; hematocrit: -20% vs 0%, P=0.03; hemoglobin: -18% vs 3%, P=0.02, respectively). In the absence of stroke (age-matched controls), SS WT had elevated HMOX1 protein compared to SS T117S , which normalized in post-stroke SS WT but was unchanged in post-stroke SS T117S . Kidney and plasma EPO levels significantly increased in SS WT post-stroke, but not in SS T117S . In vitro studies using HEK293 cells showed EPO and HMOX1 decrease with Cyb5R3 knockdown by siRNA. Conclusion: Our findings suggest a modifying role for Cyb5R3 in brain-kidney crosstalk during ischemic stroke, wherein loss of T117S Cyb5R3 activity negatively impacts renal and plasma EPO levels and resilience against infarct of ischemic brain tissue. The Cyb5R3 axis on which the brain-kidney-blood response to stroke in SCD turns represents a novel target for precision medicine approaches to managing stroke risk and pathology in SCD carriers of the T117S variant." @default.
- W4319007864 created "2023-02-03" @default.
- W4319007864 creator A5019025963 @default.
- W4319007864 creator A5028596061 @default.
- W4319007864 creator A5030955294 @default.
- W4319007864 creator A5034559313 @default.
- W4319007864 creator A5044642739 @default.
- W4319007864 creator A5076688608 @default.
- W4319007864 creator A5079581156 @default.
- W4319007864 date "2023-02-01" @default.
- W4319007864 modified "2023-09-23" @default.
- W4319007864 title "Abstract 104: Cytochrome B5 Reductase 3 Regulates The Erythropoietin Response To Ischemic Stroke In A Mouse Model Of Chronic Anemia And Oxidative Stress" @default.
- W4319007864 doi "https://doi.org/10.1161/str.54.suppl_1.104" @default.
- W4319007864 hasPublicationYear "2023" @default.
- W4319007864 type Work @default.
- W4319007864 citedByCount "0" @default.
- W4319007864 crossrefType "journal-article" @default.
- W4319007864 hasAuthorship W4319007864A5019025963 @default.
- W4319007864 hasAuthorship W4319007864A5028596061 @default.
- W4319007864 hasAuthorship W4319007864A5030955294 @default.
- W4319007864 hasAuthorship W4319007864A5034559313 @default.
- W4319007864 hasAuthorship W4319007864A5044642739 @default.
- W4319007864 hasAuthorship W4319007864A5076688608 @default.
- W4319007864 hasAuthorship W4319007864A5079581156 @default.
- W4319007864 hasConcept C126322002 @default.
- W4319007864 hasConcept C127413603 @default.
- W4319007864 hasConcept C134018914 @default.
- W4319007864 hasConcept C134651460 @default.
- W4319007864 hasConcept C181199279 @default.
- W4319007864 hasConcept C2776151105 @default.
- W4319007864 hasConcept C2776217839 @default.
- W4319007864 hasConcept C2778248108 @default.
- W4319007864 hasConcept C2778534260 @default.
- W4319007864 hasConcept C2778917026 @default.
- W4319007864 hasConcept C2780645631 @default.
- W4319007864 hasConcept C2780959883 @default.
- W4319007864 hasConcept C55493867 @default.
- W4319007864 hasConcept C71924100 @default.
- W4319007864 hasConcept C78519656 @default.
- W4319007864 hasConcept C86803240 @default.
- W4319007864 hasConceptScore W4319007864C126322002 @default.
- W4319007864 hasConceptScore W4319007864C127413603 @default.
- W4319007864 hasConceptScore W4319007864C134018914 @default.
- W4319007864 hasConceptScore W4319007864C134651460 @default.
- W4319007864 hasConceptScore W4319007864C181199279 @default.
- W4319007864 hasConceptScore W4319007864C2776151105 @default.
- W4319007864 hasConceptScore W4319007864C2776217839 @default.
- W4319007864 hasConceptScore W4319007864C2778248108 @default.
- W4319007864 hasConceptScore W4319007864C2778534260 @default.
- W4319007864 hasConceptScore W4319007864C2778917026 @default.
- W4319007864 hasConceptScore W4319007864C2780645631 @default.
- W4319007864 hasConceptScore W4319007864C2780959883 @default.
- W4319007864 hasConceptScore W4319007864C55493867 @default.
- W4319007864 hasConceptScore W4319007864C71924100 @default.
- W4319007864 hasConceptScore W4319007864C78519656 @default.
- W4319007864 hasConceptScore W4319007864C86803240 @default.
- W4319007864 hasIssue "Suppl_1" @default.
- W4319007864 hasLocation W43190078641 @default.
- W4319007864 hasOpenAccess W4319007864 @default.
- W4319007864 hasPrimaryLocation W43190078641 @default.
- W4319007864 hasRelatedWork W2068881202 @default.
- W4319007864 hasRelatedWork W2158399804 @default.
- W4319007864 hasRelatedWork W2361108265 @default.
- W4319007864 hasRelatedWork W2371572840 @default.
- W4319007864 hasRelatedWork W2378847107 @default.
- W4319007864 hasRelatedWork W2386058477 @default.
- W4319007864 hasRelatedWork W2390387684 @default.
- W4319007864 hasRelatedWork W2415599063 @default.
- W4319007864 hasRelatedWork W2805683016 @default.
- W4319007864 hasRelatedWork W4312983352 @default.
- W4319007864 hasVolume "54" @default.
- W4319007864 isParatext "false" @default.
- W4319007864 isRetracted "false" @default.
- W4319007864 workType "article" @default.