Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912695828> ?p ?o ?g. }
Showing items 1 to 64 of
64
with 100 items per page.
- W2912695828 abstract "In cardiomyocytes, signaling through RhoA is protective against ischemia/reperfusion injury. Cardioprotective receptor agonists such as sphingosine-1-phosphate (S1P) provide protection through RhoA activation. Mitochondrial fission has been suggested to play a role in cardioprotection, allowing for selective degradation of smaller damaged mitochondria. Our previous studies showed that RhoA signaling can protect cardiomyocytes against ischemia/reperfusion injury by blocking mitochondrial death pathways under oxidative stress, however it is not known if RhoA activation also regulates mitochondrial quality control. We tested the possibility that activated RhoA regulates cardiac mitochondrial fission. Adenoviral expression of constitutively active RhoA in cardiomyocytes caused an increase in small, fragmented mitochondria observed by both fluorescent confocal microscopy and electron microscopy. This mitochondrial fission phenotype was attenuated by inhibition of the downstream RhoA target Rho-associated Protein Kinase (ROCK), or by siRNA knockdown of the primary fission protein Dynamin-related Protein 1 (Drp1). Activated Drp1 causes mitochondrial fission when it translocates from the cytosol to the mitochondria, a process regulated by Drp1 phosphorylation. We determined that expression of active RhoA in cardiomyocytes stimulated phosphorylation of Drp1 at serine-616, and increased mitochondrial levels of Drp1. Both phosphorylation and mitochondrial translocation of Drp1 by active RhoA could be blocked by ROCK inhibition. Endogenous RhoA activation by S1P also increased Drp1 phosphorylation and mitochondrial translocation in a RhoA-dependent and ROCK-dependent mechanism. In conclusion, RhoA activation in cardiomyocytes can increase Drp1 phosphorylation and Drp1 mitochondrial localization, and induce mitochondrial fission. We propose that mitochondrial fission, elicited in response to increased availability of S1P and activation of RhoA in response to ischemia/reperfusion injury, represents a previously unknown pathway for cardioprotection." @default.
- W2912695828 created "2019-02-21" @default.
- W2912695828 creator A5012522794 @default.
- W2912695828 creator A5021615930 @default.
- W2912695828 creator A5045287779 @default.
- W2912695828 creator A5050891236 @default.
- W2912695828 date "2017-07-21" @default.
- W2912695828 modified "2023-09-24" @default.
- W2912695828 title "Abstract 313: Sphingosine-1-Phosphate and RhoA Signaling Regulate Dynamin-Related Protein 1 and Cardiac Mitochondrial Fission" @default.
- W2912695828 doi "https://doi.org/10.1161/res.121.suppl_1.313" @default.
- W2912695828 hasPublicationYear "2017" @default.
- W2912695828 type Work @default.
- W2912695828 sameAs 2912695828 @default.
- W2912695828 citedByCount "0" @default.
- W2912695828 crossrefType "journal-article" @default.
- W2912695828 hasAuthorship W2912695828A5012522794 @default.
- W2912695828 hasAuthorship W2912695828A5021615930 @default.
- W2912695828 hasAuthorship W2912695828A5045287779 @default.
- W2912695828 hasAuthorship W2912695828A5050891236 @default.
- W2912695828 hasConcept C104317684 @default.
- W2912695828 hasConcept C11960822 @default.
- W2912695828 hasConcept C163950672 @default.
- W2912695828 hasConcept C17619807 @default.
- W2912695828 hasConcept C185592680 @default.
- W2912695828 hasConcept C24586158 @default.
- W2912695828 hasConcept C2777093181 @default.
- W2912695828 hasConcept C2777324860 @default.
- W2912695828 hasConcept C28859421 @default.
- W2912695828 hasConcept C55493867 @default.
- W2912695828 hasConcept C62478195 @default.
- W2912695828 hasConcept C86803240 @default.
- W2912695828 hasConcept C95444343 @default.
- W2912695828 hasConceptScore W2912695828C104317684 @default.
- W2912695828 hasConceptScore W2912695828C11960822 @default.
- W2912695828 hasConceptScore W2912695828C163950672 @default.
- W2912695828 hasConceptScore W2912695828C17619807 @default.
- W2912695828 hasConceptScore W2912695828C185592680 @default.
- W2912695828 hasConceptScore W2912695828C24586158 @default.
- W2912695828 hasConceptScore W2912695828C2777093181 @default.
- W2912695828 hasConceptScore W2912695828C2777324860 @default.
- W2912695828 hasConceptScore W2912695828C28859421 @default.
- W2912695828 hasConceptScore W2912695828C55493867 @default.
- W2912695828 hasConceptScore W2912695828C62478195 @default.
- W2912695828 hasConceptScore W2912695828C86803240 @default.
- W2912695828 hasConceptScore W2912695828C95444343 @default.
- W2912695828 hasIssue "suppl_1" @default.
- W2912695828 hasLocation W29126958281 @default.
- W2912695828 hasOpenAccess W2912695828 @default.
- W2912695828 hasPrimaryLocation W29126958281 @default.
- W2912695828 hasRelatedWork W2015050897 @default.
- W2912695828 hasRelatedWork W2058290041 @default.
- W2912695828 hasRelatedWork W2059009119 @default.
- W2912695828 hasRelatedWork W2121077787 @default.
- W2912695828 hasRelatedWork W2147551208 @default.
- W2912695828 hasRelatedWork W2171278822 @default.
- W2912695828 hasRelatedWork W2559995883 @default.
- W2912695828 hasRelatedWork W2912695828 @default.
- W2912695828 hasRelatedWork W2923019118 @default.
- W2912695828 hasRelatedWork W2981431241 @default.
- W2912695828 hasVolume "121" @default.
- W2912695828 isParatext "false" @default.
- W2912695828 isRetracted "false" @default.
- W2912695828 magId "2912695828" @default.
- W2912695828 workType "article" @default.