FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1990635695> ?p ?o ?g. }

• W1990635695 endingPage "185" @default.
• W1990635695 startingPage "174" @default.
• W1990635695 abstract "Despite an established role of mitochondrial dysfunction in cardiac ischemia/reperfusion (I/R) injury, the upstream activators have remained incompletely defined. We have recently identified an innovative role of exogenously applied netrin-1 in cardioprotection, which is mediated by increased nitric oxide (NO) bioavailability. Here, we tested the hypothesis that this “pharmacological” treatment of netrin-1 preserves mitochondrial function via novel mechanisms that are NO dependent. Freshly isolated C57BL6 mouse hearts were perfused using a Langendorff system, and subjected to a 20 min global ischemia/60 min reperfusion, in the presence or absence of netrin-1. I/R induced marked increases in infarct size, total superoxide and hydrogen peroxide production, activity and protein abundance of NADPH oxidase (NOX) isoform 4 (NOX4), as well as impaired mitochondrial integrity and function, all of which were attenuated by netrin-1. This protective effect of netrin-1 is attributed to cGMP, a downstream effector of NO. The protein levels of NOX1 and NOX2 were however unaffected, and infarct size from NOX1 and NOX2 knockouts was not different from wild type animals. Scavenging of NO with PTIO reversed inhibitory effects of netrin-1 on NOX4, while NO donor attenuated NOX4 protein abundance. In vivo NOX4 RNAi, or sepiapterin perfusion, resulted in recoupling of NOS, decreased infarct size, and blockade of dysfunctional mitochondrial swelling and mitochondrial superoxide production. These data demonstrate that netrin-1 induces cardioprotection through inhibition of NOX4 activity, which leads to recoupling of NOS, augmented NO bioavailability, reduction in oxidative stress, and ultimately preservation of mitochondrial function. The NO-dependent NOX4 inhibition connects with our previously established pathway of DCC/ERK1/2/eNOS/NO/DCC feed-forward mechanism, to maintain NOS in the coupling state to attenuate oxidative stress to preserve mitochondrial function. These findings may promote development of novel therapeutics for cardiac I/R injury. This article is part of a Special Issue entitled “Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease”." @default.
• W1990635695 created "2016-06-24" @default.
• W1990635695 creator A5005482357 @default.
• W1990635695 creator A5018191047 @default.
• W1990635695 creator A5080026993 @default.
• W1990635695 creator A5088140292 @default.
• W1990635695 date "2015-01-01" @default.
• W1990635695 modified "2023-10-15" @default.
• W1990635695 title "Netrin-1 abrogates ischemia/reperfusion-induced cardiac mitochondrial dysfunction via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS" @default.
• W1990635695 cites W1630602822 @default.
• W1990635695 cites W1821918060 @default.
• W1990635695 cites W1952998189 @default.
• W1990635695 cites W1966756015 @default.
• W1990635695 cites W1971215115 @default.
• W1990635695 cites W1971556924 @default.
• W1990635695 cites W1974358158 @default.
• W1990635695 cites W1977551186 @default.
• W1990635695 cites W1982974280 @default.
• W1990635695 cites W1983229253 @default.
• W1990635695 cites W1984668546 @default.
• W1990635695 cites W1994365742 @default.
• W1990635695 cites W2001422785 @default.
• W1990635695 cites W2002629623 @default.
• W1990635695 cites W2003937760 @default.
• W1990635695 cites W2007418718 @default.
• W1990635695 cites W2007883033 @default.
• W1990635695 cites W2008960727 @default.
• W1990635695 cites W2009616384 @default.
• W1990635695 cites W2026685522 @default.
• W1990635695 cites W2032203291 @default.
• W1990635695 cites W2033192971 @default.
• W1990635695 cites W2034340179 @default.
• W1990635695 cites W2034418321 @default.
• W1990635695 cites W2044411411 @default.
• W1990635695 cites W2051909997 @default.
• W1990635695 cites W2056852634 @default.
• W1990635695 cites W2058618487 @default.
• W1990635695 cites W2060015752 @default.
• W1990635695 cites W2062976933 @default.
• W1990635695 cites W2066418551 @default.
• W1990635695 cites W2074800090 @default.
• W1990635695 cites W2077916251 @default.
• W1990635695 cites W2088759134 @default.
• W1990635695 cites W2095221846 @default.
• W1990635695 cites W2101877073 @default.
• W1990635695 cites W2107554716 @default.
• W1990635695 cites W2111579090 @default.
• W1990635695 cites W2112540241 @default.
• W1990635695 cites W2120409506 @default.
• W1990635695 cites W2126788226 @default.
• W1990635695 cites W2128045871 @default.
• W1990635695 cites W2129048293 @default.
• W1990635695 cites W2135314348 @default.
• W1990635695 cites W2135412628 @default.
• W1990635695 cites W2148030708 @default.
• W1990635695 cites W2165389421 @default.
• W1990635695 cites W2416074078 @default.
• W1990635695 cites W31761959 @default.
• W1990635695 doi "https://doi.org/10.1016/j.yjmcc.2014.07.005" @default.
• W1990635695 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4268247" @default.
• W1990635695 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25066694" @default.
• W1990635695 hasPublicationYear "2015" @default.
• W1990635695 type Work @default.
• W1990635695 sameAs 1990635695 @default.
• W1990635695 citedByCount "44" @default.
• W1990635695 countsByYear W19906356952015 @default.
• W1990635695 countsByYear W19906356952016 @default.
• W1990635695 countsByYear W19906356952017 @default.
• W1990635695 countsByYear W19906356952018 @default.
• W1990635695 countsByYear W19906356952019 @default.
• W1990635695 countsByYear W19906356952020 @default.
• W1990635695 countsByYear W19906356952021 @default.
• W1990635695 countsByYear W19906356952022 @default.
• W1990635695 crossrefType "journal-article" @default.
• W1990635695 hasAuthorship W1990635695A5005482357 @default.
• W1990635695 hasAuthorship W1990635695A5018191047 @default.
• W1990635695 hasAuthorship W1990635695A5080026993 @default.
• W1990635695 hasAuthorship W1990635695A5088140292 @default.
• W1990635695 hasBestOaLocation W19906356952 @default.
• W1990635695 hasConcept C126322002 @default.
• W1990635695 hasConcept C178790620 @default.
• W1990635695 hasConcept C181199279 @default.
• W1990635695 hasConcept C185592680 @default.
• W1990635695 hasConcept C2776151105 @default.
• W1990635695 hasConcept C2778784160 @default.
• W1990635695 hasConcept C2779676291 @default.
• W1990635695 hasConcept C2779719074 @default.
• W1990635695 hasConcept C2779765511 @default.
• W1990635695 hasConcept C2780114680 @default.
• W1990635695 hasConcept C2780795997 @default.
• W1990635695 hasConcept C28859421 @default.
• W1990635695 hasConcept C519581460 @default.
• W1990635695 hasConcept C541997718 @default.
• W1990635695 hasConcept C55493867 @default.
• W1990635695 hasConcept C71924100 @default.
• W1990635695 hasConcept C86803240 @default.
• W1990635695 hasConcept C95444343 @default.
• W1990635695 hasConcept C98274493 @default.

• next