Simple view
Full metadata view
Authors
Statistics
Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells : a role for
carbon monoxide
CO-RM
endothelium
glycolysis
mitochondrial BKCa channels
oxidative phosphorylation
respiration
benzyloxycarbonylleucylleucylleucinal
calcium channel
carbon monoxide
large conductance calcium activated potassium channel
paxilline
potassium channel
proton
acidification
article
controlled study
electron spin resonance
endothelium cell
glycolysis
human
human cell
metabolism
mitochondrial respiration
oxidative phosphorylation
oxidative phosphorylation uncoupling
oxygen consumption
patch clamp technique
priority journal
Abstract Carbon monoxide (CO), a product of heme degradation by heme oxygenases, plays an important role in vascular homeostasis. Recent evidence indicates that mitochondria are among a number of molecular targets that mediate the cellular actions of CO. In the present study we characterized the effects of CO released from CORM-401 on mitochondrial respiration and glycolysis in intact human endothelial cells using electron paramagnetic resonance (EPR) oximetry and the Seahorse XF technology. We found that CORM-401 (10-100
cris.lastimport.wos | 2024-04-09T18:29:00Z | |
dc.abstract.en | Abstract Carbon monoxide (CO), a product of heme degradation by heme oxygenases, plays an important role in vascular homeostasis. Recent evidence indicates that mitochondria are among a number of molecular targets that mediate the cellular actions of CO. In the present study we characterized the effects of CO released from CORM-401 on mitochondrial respiration and glycolysis in intact human endothelial cells using electron paramagnetic resonance (EPR) oximetry and the Seahorse XF technology. We found that CORM-401 (10-100 $\mu$M) induced a persistent increase in the oxygen consumption rate (OCR) that was accompanied by inhibition of glycolysis (extracellular acidification rate, ECAR) and a decrease in ATP-turnover. Furthermore, CORM-401 increased proton leak, diminished mitochondrial reserve capacity and enhanced non-mitochondrial respiration. Inactive CORM-401 (iCORM-401) neither induced mitochondrial uncoupling nor inhibited glycolysis, supporting a direct role of CO in the endothelial metabolic response induced by CORM-401. Interestingly, blockade of mitochondrial large-conductance calcium-regulated potassium ion channels ($mitoBK_{Ca}$) with paxilline abolished the increase in OCR promoted by CORM-401 without affecting ECAR; patch-clamp experiments confirmed that CO derived from CORM-401 activated $mitoBK_{Ca}$ channels present in mitochondria. Conversely, stabilization of glycolysis by MG132 prevented CORM-401-mediated decrease in ECAR but did not modify the OCR response. In summary, we demonstrated in intact endothelial cells that CO induces a two-component metabolic response: uncoupling of mitochondrial respiration dependent on the activation of $mitoBK_{Ca}$ channels and inhibition of glycolysis independent of $mitoBK_{Ca}$ channels. | pl |
dc.affiliation | Pion Rektora : Jagiellońskie Centrum Rozwoju Leków | pl |
dc.contributor.author | Kaczara, Patrycja - 200164 | pl |
dc.contributor.author | Motterlini, Roberto | pl |
dc.contributor.author | Rosen, Gerald M. | pl |
dc.contributor.author | Augustynek, Bartłomiej | pl |
dc.contributor.author | Bednarczyk, Piotr | pl |
dc.contributor.author | Szewczyk, Adam | pl |
dc.contributor.author | Foresti, Roberta | pl |
dc.contributor.author | Chłopicki, Stefan - 128995 | pl |
dc.date.accessioned | 2016-08-22T08:56:00Z | |
dc.date.available | 2016-08-22T08:56:00Z | |
dc.date.issued | 2015 | pl |
dc.description.number | 10 | pl |
dc.description.physical | 1297-1309 | pl |
dc.description.points | 40 | pl |
dc.description.volume | 1847 | pl |
dc.identifier.doi | 10.1016/j.bbabio.2015.07.004 | pl |
dc.identifier.eissn | 1879-2650 | pl |
dc.identifier.issn | 0005-2728 | pl |
dc.identifier.uri | http://ruj.uj.edu.pl/xmlui/handle/item/29758 | |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.rights | Dodaję tylko opis bibliograficzny | * |
dc.rights.licence | bez licencji | |
dc.rights.uri | * | |
dc.subject.en | carbon monoxide | pl |
dc.subject.en | CO-RM | pl |
dc.subject.en | endothelium | pl |
dc.subject.en | glycolysis | pl |
dc.subject.en | mitochondrial BKCa channels | pl |
dc.subject.en | oxidative phosphorylation | pl |
dc.subject.en | respiration | pl |
dc.subject.en | benzyloxycarbonylleucylleucylleucinal | pl |
dc.subject.en | calcium channel | pl |
dc.subject.en | carbon monoxide | pl |
dc.subject.en | large conductance calcium activated potassium channel | pl |
dc.subject.en | paxilline | pl |
dc.subject.en | potassium channel | pl |
dc.subject.en | proton | pl |
dc.subject.en | acidification | pl |
dc.subject.en | article | pl |
dc.subject.en | controlled study | pl |
dc.subject.en | electron spin resonance | pl |
dc.subject.en | endothelium cell | pl |
dc.subject.en | glycolysis | pl |
dc.subject.en | human | pl |
dc.subject.en | human cell | pl |
dc.subject.en | metabolism | pl |
dc.subject.en | mitochondrial respiration | pl |
dc.subject.en | oxidative phosphorylation | pl |
dc.subject.en | oxidative phosphorylation uncoupling | pl |
dc.subject.en | oxygen consumption | pl |
dc.subject.en | patch clamp technique | pl |
dc.subject.en | priority journal | pl |
dc.subtype | Article | pl |
dc.title | Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells : a role for $mitoBK_{Ca}$ channels | pl |
dc.title.journal | Biochimica et Biophysica Acta. Bioenergetics | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |