Matches in SemOpenAlex for { <https://semopenalex.org/work/W3100657228> ?p ?o ?g. }
Showing items 1 to 66 of
66
with 100 items per page.
- W3100657228 abstract "Introduction: Myocardial infarction (MI) is characterized by cardiac dysfunction and increased cardiomyocyte death, induced mainly by apoptosis. Using an unbiased transcriptome analysis, we identified flavin containing monooxygenase 2 (FMO2) as one of the top-ranked genes involved in the process of MI. In this study, we investigate the roles of FMO2 in ischemic injury and its potential mechanisms. Hypothesis: FMO2 exhibits the cardiac protection from MI injury. Methods: Male SD rats receiving either adeno-associated virus serotype 9 containing FMO2 shRNA particles (AAV-shFMO2) or FMO2 (AAV-FMO2), and FMO2 knockout rats were subjected to myocardial infarction surgery. Cardiac function, fibrosis, and apoptosis were examined in these rats and related cellular and molecular mechanisms were investigated. Results: Cardiac ischemia injury was associated with significant increases of FMO2 levels both in ex vivo and in vivo models. Loss of FMO2 significantly enhanced cardiomyocyte apoptosis and deteriorated cardiac function accompanied by augmented infarct size in infarcted rat hearts, while elevated expression of FMO2 exhibited the opposite results. Mechanically, located on the ER membrane, FMO2 inhibited activation of ER stress-initiated apoptotic proteins including caspase 12 and C/EBP homologous protein (CHOP), via down-regulating upstream unfolded protein response (UPR) pathway. Furthermore, we found that FMO2, as a novel chaperone in ER, directly catalyzed disulfide-bond synthesis to facilitate proteins folding. Finally, structure analysis of FMO2 revealed the active site GVSG for disulfide-bond catalysis, which was confirmed by the molecular docking experiment of GSH with FMO2. However, FMO2 with GVSG mutation failed to catalyze disulfide-bond formation and lost protection from ER stress or apoptosis in cardiomyocytes. Conclusion: FMO2 confers cardiac protection from ischemic damage due to improved cardiomyocyte apoptosis through UPR pathway, which is mediated by disulfide-bond catalysis at GVSG active site. Our findings uncover a novel FMO2-involved regulatory mechanism which could serves as a potential therapeutic target for ischemic cardiovascular diseases." @default.
- W3100657228 created "2020-11-23" @default.
- W3100657228 creator A5001395097 @default.
- W3100657228 creator A5001861759 @default.
- W3100657228 creator A5008964504 @default.
- W3100657228 creator A5019443348 @default.
- W3100657228 creator A5027850301 @default.
- W3100657228 creator A5031461345 @default.
- W3100657228 creator A5033946637 @default.
- W3100657228 creator A5042049792 @default.
- W3100657228 creator A5042765146 @default.
- W3100657228 creator A5045728477 @default.
- W3100657228 creator A5053406390 @default.
- W3100657228 creator A5068368466 @default.
- W3100657228 creator A5073679286 @default.
- W3100657228 creator A5087944559 @default.
- W3100657228 creator A5089893897 @default.
- W3100657228 date "2020-11-17" @default.
- W3100657228 modified "2023-10-16" @default.
- W3100657228 title "Abstract 210: Flavin Containing Monooxygenase 2 Confers Cardiac Protection via Unfolded Protein Response Signaling Modulated by Disulfide Bond Catalysis" @default.
- W3100657228 doi "https://doi.org/10.1161/circ.142.suppl_4.210" @default.
- W3100657228 hasPublicationYear "2020" @default.
- W3100657228 type Work @default.
- W3100657228 sameAs 3100657228 @default.
- W3100657228 citedByCount "0" @default.
- W3100657228 crossrefType "journal-article" @default.
- W3100657228 hasAuthorship W3100657228A5001395097 @default.
- W3100657228 hasAuthorship W3100657228A5001861759 @default.
- W3100657228 hasAuthorship W3100657228A5008964504 @default.
- W3100657228 hasAuthorship W3100657228A5019443348 @default.
- W3100657228 hasAuthorship W3100657228A5027850301 @default.
- W3100657228 hasAuthorship W3100657228A5031461345 @default.
- W3100657228 hasAuthorship W3100657228A5033946637 @default.
- W3100657228 hasAuthorship W3100657228A5042049792 @default.
- W3100657228 hasAuthorship W3100657228A5042765146 @default.
- W3100657228 hasAuthorship W3100657228A5045728477 @default.
- W3100657228 hasAuthorship W3100657228A5053406390 @default.
- W3100657228 hasAuthorship W3100657228A5068368466 @default.
- W3100657228 hasAuthorship W3100657228A5073679286 @default.
- W3100657228 hasAuthorship W3100657228A5087944559 @default.
- W3100657228 hasAuthorship W3100657228A5089893897 @default.
- W3100657228 hasConcept C185592680 @default.
- W3100657228 hasConcept C55493867 @default.
- W3100657228 hasConcept C71924100 @default.
- W3100657228 hasConceptScore W3100657228C185592680 @default.
- W3100657228 hasConceptScore W3100657228C55493867 @default.
- W3100657228 hasConceptScore W3100657228C71924100 @default.
- W3100657228 hasIssue "Suppl_4" @default.
- W3100657228 hasLocation W31006572281 @default.
- W3100657228 hasOpenAccess W3100657228 @default.
- W3100657228 hasPrimaryLocation W31006572281 @default.
- W3100657228 hasRelatedWork W1531601525 @default.
- W3100657228 hasRelatedWork W2319480705 @default.
- W3100657228 hasRelatedWork W2384464875 @default.
- W3100657228 hasRelatedWork W2606230654 @default.
- W3100657228 hasRelatedWork W2607424097 @default.
- W3100657228 hasRelatedWork W2748952813 @default.
- W3100657228 hasRelatedWork W2899084033 @default.
- W3100657228 hasRelatedWork W2948807893 @default.
- W3100657228 hasRelatedWork W3031052312 @default.
- W3100657228 hasRelatedWork W2778153218 @default.
- W3100657228 hasVolume "142" @default.
- W3100657228 isParatext "false" @default.
- W3100657228 isRetracted "false" @default.
- W3100657228 magId "3100657228" @default.
- W3100657228 workType "article" @default.