FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2019950737> ?p ?o ?g. }

• W2019950737 endingPage "31992" @default.
• W2019950737 startingPage "31984" @default.
• W2019950737 abstract "The cardiac Na+/Ca2+ exchanger (NCX) is the major Ca2+ efflux pathway on the sarcolemma, counterbalancing Ca2+ influx via L-type Ca2+ current during excitation-contraction coupling. Altered NCX activity modulates the sarcoplastic reticulum Ca2+ load and can contribute to abnormal Ca2+ handling and arrhythmias. NADH/NAD+ is the main redox couple controlling mitochondrial energy production, glycolysis, and other redox reactions. Here, we tested whether cytosolic NADH/NAD+ redox potential regulates NCX activity in adult cardiomyocytes. NCX current (INCX), measured with whole cell patch clamp, was inhibited in response to cytosolic NADH loaded directly via pipette or increased by extracellular lactate perfusion, whereas an increase of mitochondrial NADH had no effect. Reactive oxygen species (ROS) accumulation was enhanced by increasing cytosolic NADH, and NADH-induced INCX inhibition was abolished by the H2O2 scavenger catalase. NADH-induced ROS accumulation was independent of mitochondrial respiration (rotenone-insensitive) but was inhibited by the flavoenzyme blocker diphenylene iodonium. NADPH oxidase was ruled out as the effector because INCX was insensitive to cytosolic NADPH, and NADH-induced ROS and INCX inhibition were not abrogated by the specific NADPH oxidase inhibitor gp91ds-tat. This study reveals a novel mechanism of NCX regulation by cytosolic NADH/NAD+ redox potential through a ROS-generating NADH-driven flavoprotein oxidase. The mechanism is likely to play a key role in Ca2+ homeostasis and the response to alterations in the cytosolic pyridine nucleotide redox state during ischemia-reperfusion or other cardiovascular diseases.Background: Regulation of the sarcolemmal Na+/Ca2+ exchanger (NCX) modulates cardiac excitation-contraction coupling, and NCX contributes to ischemia-reperfusion injury.Results: Increased cytosolic NADH inhibits NCX through a ROS-dependent mechanism.Conclusion: Regulation by cytosolic NADH reveals a novel way that NCX responds to changes in energy metabolism.Significance: NADH-dependent regulation of NCX regulation represents a potential therapeutic target for ameliorating ischemia-reperfusion injury or chronic cardiovascular disease. The cardiac Na+/Ca2+ exchanger (NCX) is the major Ca2+ efflux pathway on the sarcolemma, counterbalancing Ca2+ influx via L-type Ca2+ current during excitation-contraction coupling. Altered NCX activity modulates the sarcoplastic reticulum Ca2+ load and can contribute to abnormal Ca2+ handling and arrhythmias. NADH/NAD+ is the main redox couple controlling mitochondrial energy production, glycolysis, and other redox reactions. Here, we tested whether cytosolic NADH/NAD+ redox potential regulates NCX activity in adult cardiomyocytes. NCX current (INCX), measured with whole cell patch clamp, was inhibited in response to cytosolic NADH loaded directly via pipette or increased by extracellular lactate perfusion, whereas an increase of mitochondrial NADH had no effect. Reactive oxygen species (ROS) accumulation was enhanced by increasing cytosolic NADH, and NADH-induced INCX inhibition was abolished by the H2O2 scavenger catalase. NADH-induced ROS accumulation was independent of mitochondrial respiration (rotenone-insensitive) but was inhibited by the flavoenzyme blocker diphenylene iodonium. NADPH oxidase was ruled out as the effector because INCX was insensitive to cytosolic NADPH, and NADH-induced ROS and INCX inhibition were not abrogated by the specific NADPH oxidase inhibitor gp91ds-tat. This study reveals a novel mechanism of NCX regulation by cytosolic NADH/NAD+ redox potential through a ROS-generating NADH-driven flavoprotein oxidase. The mechanism is likely to play a key role in Ca2+ homeostasis and the response to alterations in the cytosolic pyridine nucleotide redox state during ischemia-reperfusion or other cardiovascular diseases. Background: Regulation of the sarcolemmal Na+/Ca2+ exchanger (NCX) modulates cardiac excitation-contraction coupling, and NCX contributes to ischemia-reperfusion injury. Results: Increased cytosolic NADH inhibits NCX through a ROS-dependent mechanism. Conclusion: Regulation by cytosolic NADH reveals a novel way that NCX responds to changes in energy metabolism. Significance: NADH-dependent regulation of NCX regulation represents a potential therapeutic target for ameliorating ischemia-reperfusion injury or chronic cardiovascular disease." @default.
• W2019950737 created "2016-06-24" @default.
• W2019950737 creator A5071555900 @default.
• W2019950737 creator A5080198568 @default.
• W2019950737 date "2013-11-01" @default.
• W2019950737 modified "2023-10-12" @default.
• W2019950737 title "Regulation of the Na+/Ca2+ Exchanger by Pyridine Nucleotide Redox Potential in Ventricular Myocytes" @default.
• W2019950737 cites W1530888481 @default.
• W2019950737 cites W1665675901 @default.
• W2019950737 cites W1738677317 @default.
• W2019950737 cites W184224711 @default.
• W2019950737 cites W1965035060 @default.
• W2019950737 cites W1975829062 @default.
• W2019950737 cites W1982732769 @default.
• W2019950737 cites W1986088683 @default.
• W2019950737 cites W1990674615 @default.
• W2019950737 cites W1990992520 @default.
• W2019950737 cites W1993208368 @default.
• W2019950737 cites W1994387603 @default.
• W2019950737 cites W1997677285 @default.
• W2019950737 cites W2005871976 @default.
• W2019950737 cites W2009601122 @default.
• W2019950737 cites W2014900951 @default.
• W2019950737 cites W2015406042 @default.
• W2019950737 cites W2026696517 @default.
• W2019950737 cites W2031696737 @default.
• W2019950737 cites W2033590169 @default.
• W2019950737 cites W2036219577 @default.
• W2019950737 cites W2043883936 @default.
• W2019950737 cites W2045197162 @default.
• W2019950737 cites W2050101609 @default.
• W2019950737 cites W2052613080 @default.
• W2019950737 cites W2067275294 @default.
• W2019950737 cites W2071782902 @default.
• W2019950737 cites W2079310705 @default.
• W2019950737 cites W2081926380 @default.
• W2019950737 cites W2082208569 @default.
• W2019950737 cites W2082879125 @default.
• W2019950737 cites W2089263288 @default.
• W2019950737 cites W2096545094 @default.
• W2019950737 cites W2109632370 @default.
• W2019950737 cites W2116884436 @default.
• W2019950737 cites W2120939977 @default.
• W2019950737 cites W2123462780 @default.
• W2019950737 cites W2128678804 @default.
• W2019950737 cites W2128801406 @default.
• W2019950737 cites W2132223552 @default.
• W2019950737 cites W2142057607 @default.
• W2019950737 cites W2143183540 @default.
• W2019950737 cites W2147602331 @default.
• W2019950737 cites W2147959747 @default.
• W2019950737 cites W2152700015 @default.
• W2019950737 cites W2153374355 @default.
• W2019950737 cites W2165537841 @default.
• W2019950737 cites W2189362830 @default.
• W2019950737 cites W2335300675 @default.
• W2019950737 cites W4236653206 @default.
• W2019950737 cites W2103852194 @default.
• W2019950737 doi "https://doi.org/10.1074/jbc.m113.496588" @default.
• W2019950737 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3814794" @default.
• W2019950737 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24045952" @default.
• W2019950737 hasPublicationYear "2013" @default.
• W2019950737 type Work @default.
• W2019950737 sameAs 2019950737 @default.
• W2019950737 citedByCount "26" @default.
• W2019950737 countsByYear W20199507372013 @default.
• W2019950737 countsByYear W20199507372014 @default.
• W2019950737 countsByYear W20199507372015 @default.
• W2019950737 countsByYear W20199507372016 @default.
• W2019950737 countsByYear W20199507372017 @default.
• W2019950737 countsByYear W20199507372018 @default.
• W2019950737 countsByYear W20199507372019 @default.
• W2019950737 countsByYear W20199507372020 @default.
• W2019950737 countsByYear W20199507372021 @default.
• W2019950737 countsByYear W20199507372022 @default.
• W2019950737 countsByYear W20199507372023 @default.
• W2019950737 crossrefType "journal-article" @default.
• W2019950737 hasAuthorship W2019950737A5071555900 @default.
• W2019950737 hasAuthorship W2019950737A5080198568 @default.
• W2019950737 hasBestOaLocation W20199507371 @default.
• W2019950737 hasConcept C12554922 @default.
• W2019950737 hasConcept C181199279 @default.
• W2019950737 hasConcept C185592680 @default.
• W2019950737 hasConcept C199096232 @default.
• W2019950737 hasConcept C20251656 @default.
• W2019950737 hasConcept C2778175917 @default.
• W2019950737 hasConcept C2779719074 @default.
• W2019950737 hasConcept C28859421 @default.
• W2019950737 hasConcept C41625074 @default.
• W2019950737 hasConcept C48349386 @default.
• W2019950737 hasConcept C55493867 @default.
• W2019950737 hasConcept C62231903 @default.
• W2019950737 hasConcept C75520062 @default.
• W2019950737 hasConcept C86803240 @default.
• W2019950737 hasConcept C95444343 @default.
• W2019950737 hasConcept C98539663 @default.
• W2019950737 hasConceptScore W2019950737C12554922 @default.
• W2019950737 hasConceptScore W2019950737C181199279 @default.

• next