FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3174026444> ?p ?o ?g. }

• W3174026444 abstract "Rationale Muscle weakness in response to chemotherapy is thought to be related to mitochondrial dysfunction. However, the underlying mechanisms by which chemotherapy alters mitochondrial bioenergetics remain unknown, but are likely unique to different types of these cytotoxic compounds. Taxanes (eg. Paclitaxel) and vinka alkaloids (eg. Vinblastine) prevent cancer cell mitosis by stabilizing and destabilizing microtubules, respectively. In mature muscle fibres (ie. non-mitotic), microtubules are thought to regulate mitochondrial bioenergetics by directly binding the ADP/ATP exchanger voltage dependent anion channel (VDAC) on the outer mitochondrial membrane. As ADP simultaneously regulates oxidative phosphorylation and oxidant generation by modulation of membrane potential, we hypothesized that manipulating microtubule architecture with paclitaxel and vinblastine would alter tubulin-VDAC interactions and influence ADP-dependent respiration and H2O2 emission. As VDAC is thought to be involved in the formation of the mitochondrial permeability transition pore (mPTP) under calcium stress, we also hypothesized that these compounds would alter mitochondrial calcium retention capacity (CRC) required for mPTP formation. Methods : Single muscle fibres and permeabilized fibre bundles were isolated from rat extensor digitorum longus muscles and incubated in paclitaxel (2hr) and vinblastine (1hr) at 4°C prior to assessing protein-protein interactions (proximity ligation assay) and mitochondrial bioenergetics. Results Paclitaxel increased both a- (p=0.01) and bII-tubulin (p=0.01) interactions with VDAC2 which was associated with a decreased ability of ADP to attenuate H2O2 emission (main effect, p=0.0006) despite no effect on ADP-stimulated respiration or CRC. In contrast, vinblastine had no effect on the amount of a- and bII-tubulin interactions with VDAC but still increased ADP-stimulated respiration (main effect, p= 0.006), decreased the ability of ADP to attenuate H2O2 emission (main effect, p=0.002) and sensitized mPTP formation as demonstrated by reduced CRC (p=0.04). Conclusion and Discussion The results demonstrate that both microtubule stabilizing and destabilizing chemotherapies cause diverse mitochondrial dysfunctions which may provide insight into their detrimental effects on muscle function. Collectively, these findings partially support the tubulin-VDAC model of regulating mitochondrial bioenergetics but suggests that microtubule architecture may also regulate mitochondrial function in mature muscle fibres through additional mechanisms. Support or Funding Information Funding was provided to C.G.R.P. by National Science and Engineering Research Council (#436138-2013) with infrastructure supported by Canada Foundation for Innovation, Ontario Research Fund and the James H. Cummings Foundation. S.V.R was supported by Ontario Graduate Scholarship. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
• W3174026444 created "2021-07-05" @default.
• W3174026444 creator A5015860052 @default.
• W3174026444 creator A5040492624 @default.
• W3174026444 date "2019-04-01" @default.
• W3174026444 modified "2023-09-27" @default.
• W3174026444 title "Altered Skeletal Muscle Microtubule‐Mitochondrial Voltage Gated‐Dependent Anion Channel (VDAC) 2 Binding is Related to Bioenergetic Impairments after Paclitaxel but not Vinblastine Chemotherapies" @default.
• W3174026444 doi "https://doi.org/10.1096/fasebj.2019.33.1_supplement.868.7" @default.
• W3174026444 hasPublicationYear "2019" @default.
• W3174026444 type Work @default.
• W3174026444 sameAs 3174026444 @default.
• W3174026444 citedByCount "0" @default.
• W3174026444 crossrefType "journal-article" @default.
• W3174026444 hasAuthorship W3174026444A5015860052 @default.
• W3174026444 hasAuthorship W3174026444A5040492624 @default.
• W3174026444 hasConcept C100206155 @default.
• W3174026444 hasConcept C104317684 @default.
• W3174026444 hasConcept C12554922 @default.
• W3174026444 hasConcept C13591479 @default.
• W3174026444 hasConcept C146587185 @default.
• W3174026444 hasConcept C185592680 @default.
• W3174026444 hasConcept C190283241 @default.
• W3174026444 hasConcept C200784783 @default.
• W3174026444 hasConcept C20418707 @default.
• W3174026444 hasConcept C2776694085 @default.
• W3174026444 hasConcept C2777132456 @default.
• W3174026444 hasConcept C2777292972 @default.
• W3174026444 hasConcept C28859421 @default.
• W3174026444 hasConcept C31573885 @default.
• W3174026444 hasConcept C54355233 @default.
• W3174026444 hasConcept C547475151 @default.
• W3174026444 hasConcept C55493867 @default.
• W3174026444 hasConcept C84425145 @default.
• W3174026444 hasConcept C86803240 @default.
• W3174026444 hasConcept C95444343 @default.
• W3174026444 hasConceptScore W3174026444C100206155 @default.
• W3174026444 hasConceptScore W3174026444C104317684 @default.
• W3174026444 hasConceptScore W3174026444C12554922 @default.
• W3174026444 hasConceptScore W3174026444C13591479 @default.
• W3174026444 hasConceptScore W3174026444C146587185 @default.
• W3174026444 hasConceptScore W3174026444C185592680 @default.
• W3174026444 hasConceptScore W3174026444C190283241 @default.
• W3174026444 hasConceptScore W3174026444C200784783 @default.
• W3174026444 hasConceptScore W3174026444C20418707 @default.
• W3174026444 hasConceptScore W3174026444C2776694085 @default.
• W3174026444 hasConceptScore W3174026444C2777132456 @default.
• W3174026444 hasConceptScore W3174026444C2777292972 @default.
• W3174026444 hasConceptScore W3174026444C28859421 @default.
• W3174026444 hasConceptScore W3174026444C31573885 @default.
• W3174026444 hasConceptScore W3174026444C54355233 @default.
• W3174026444 hasConceptScore W3174026444C547475151 @default.
• W3174026444 hasConceptScore W3174026444C55493867 @default.
• W3174026444 hasConceptScore W3174026444C84425145 @default.
• W3174026444 hasConceptScore W3174026444C86803240 @default.
• W3174026444 hasConceptScore W3174026444C95444343 @default.
• W3174026444 hasFunder F4320306666 @default.
• W3174026444 hasIssue "S1" @default.
• W3174026444 hasLocation W31740264441 @default.
• W3174026444 hasOpenAccess W3174026444 @default.
• W3174026444 hasPrimaryLocation W31740264441 @default.
• W3174026444 hasRelatedWork W1971541628 @default.
• W3174026444 hasRelatedWork W1988369885 @default.
• W3174026444 hasRelatedWork W2034188592 @default.
• W3174026444 hasRelatedWork W2103874914 @default.
• W3174026444 hasRelatedWork W2517538690 @default.
• W3174026444 hasRelatedWork W2587790007 @default.
• W3174026444 hasRelatedWork W2910524550 @default.
• W3174026444 hasRelatedWork W2952449048 @default.
• W3174026444 hasRelatedWork W3174026444 @default.
• W3174026444 hasRelatedWork W4319216264 @default.
• W3174026444 hasVolume "33" @default.
• W3174026444 isParatext "false" @default.
• W3174026444 isRetracted "false" @default.
• W3174026444 magId "3174026444" @default.
• W3174026444 workType "article" @default.