l-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: a double-edged sword phenomenon

Tuboly, Eszter; Gáspár, Renáta; Ibor, Miguel Olias; Gömöri, Kamilla; Kiss, Bernadett; Strifler, Gerda; Hartmann, Petra; Ferdinándy, Péter; Barteková, Monika; Boros, Mihály; Görbe, Anikó

doi:10.1007/s11010-019-03580-1

Cited by 13 publications

(14 citation statements)

References 35 publications

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“…Previous studies have shown that glycerophosphocholine (GPC) can reserve mitochondrial respiration, reduce ischemia-induced oxidative stress and decrease radical production [ 41 , 42 , 43 ]. Furthermore, cytoprotective effects of short-term GPC treatment have been observed in cardiac myocytes [ 44 ], including physiological balance of ROS production and cell viability. In our study, the levels of GPC were down-regulated in the aVMC and DCM stages.…”

Section: Discussionmentioning

confidence: 99%

NMR-Based Metabolomic Analysis of Sera in Mouse Models of CVB3-Induced Viral Myocarditis and Dilated Cardiomyopathy

Kong

et al. 2022

Biomolecules

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Viral myocarditis (VMC) is an inflammatory heart condition which can induce dilated cardiomyopathy (DCM). However, molecular mechanisms underlying the progression of VMC into DCM remain exclusive. Here, we established mouse models of VMC and DCM by infecting male BALB/c mice with Coxsackievirus B3 (CVB3), and performed NMR-based metabonomic analyses of mouse sera. The mouse models covered three pathological stages including: acute VMC (aVMC), chronic VMC (cVMC) and DCM. We recorded 1D 1H-NMR spectra on serum samples and conducted multivariate statistical analysis on the NMR data. We found that metabolic profiles of these three pathological stages were distinct from their normal controls (CON), and identified significant metabolites primarily responsible for the metabolic distinctions. We identified significantly disturbed metabolic pathways in the aVMC, cVMC and DCM stages relative to CON, including: taurine and hypotaurine metabolism; pyruvate metabolism; glycine, serine and threonine metabolism; glycerolipid metabolism. Additionally, we identified potential biomarkers for discriminating a VMC, cVMC and DCM from CON including: taurine, valine and acetate for aVMC; glycerol, valine and leucine for cVMC; citrate, glycine and isoleucine for DCM. This work lays the basis for mechanistically understanding the progression from acute VMC to DCM, and is beneficial to exploitation of potential biomarkers for prognosis and diagnosis of heart diseases.

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Section: Discussionmentioning

confidence: 99%

NMR-Based Metabolomic Analysis of Sera in Mouse Models of CVB3-Induced Viral Myocarditis and Dilated Cardiomyopathy

Kong

et al. 2022

Biomolecules

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“…In contrast to most changed metabolites in peripheral insulin resistance, glycerophosphorylcholine had a higher abundance in the non-insulin resistant group. This metabolite has been shown to have beneficial or detrimental effects on cell survival in primary rat cardiomyocytes, depending on the time of exposure [ 30 ]. In addition, this metabolite has been shown to reduce oxidative stress in rat liver cells by preserving mitochondrial complex 1 function [ 31 ] and can also protect against cardiac ischemia–reperfusion damage in vivo [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…This metabolite has been shown to have beneficial or detrimental effects on cell survival in primary rat cardiomyocytes, depending on the time of exposure [ 30 ]. In addition, this metabolite has been shown to reduce oxidative stress in rat liver cells by preserving mitochondrial complex 1 function [ 31 ] and can also protect against cardiac ischemia–reperfusion damage in vivo [ 30 ]. As particularly peripheral insulin resistance in MetSyn contributes to the development of insulin resistance [ 32 ], this metabolite might also protect against oxidative stress in MetSyn, which then ameliorates the progression of insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk

et al. 2021

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Metabolic syndrome (MetSyn) is an important risk factor for type 2 diabetes and cardiovascular diseases (CVD). This study aimed to find distinct plasma metabolite profiles between insulin-resistant and non-insulin resistant subjects with MetSyn and evaluate if MetSyn metabolite profiles are related to CVD risk and lipid fluxes. In a cross-sectional study, untargeted metabolomics of treatment-naive males with MetSyn (n = 132) were analyzed together with clinical parameters. In a subset of MetSyn participants, CVD risk was calculated using the Framingham score (n = 111), and lipolysis (n = 39) was measured by a two-step hyperinsulinemic euglycemic clamp using [1,1,2,3,3-2H5] glycerol to calculate lipolysis suppression rates. Peripheral insulin resistance was related to fatty acid metabolism and glycerolphosphorylcholine. Interestingly, although insulin resistance is considered to be a risk factor for CVD, we observed that there was little correspondence between metabolites associated with insulin resistance and metabolites associated with CVD risk. The latter mainly belonged to the androgenic steroid, fatty acid, phosphatidylethanolamine, and phophatidylcholine pathways. These data provide new insights into metabolic changes in mild MetSyn pathophysiology and MetSyn CVD risk related to lipid metabolism. Prospective studies may focus on the pathophysiological role of the here-identified biomarkers.

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“…Then the PI solution was replaced with fresh PBS and fluorescence intensity of each well was detected; scan matrix: 10 × 10; scan diameter: 10mm; bottom optic; no of flashes/scan point: 3; temp: 37 • C; excitation wavelength: 544 nm; emission wavelength: 610 nm. The cytoprotective effect of different compounds was compared to simulated ischemic control groups [65].…”

Section: Cell Viability Assaymentioning

confidence: 99%

Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury

et al. 2020

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Search for new cardioprotective therapies is of great importance since no cardioprotective drugs are available on the market. In line with this need, several natural biomolecules have been extensively tested for their potential cardioprotective effects. Previously, we have shown that biglycan, a member of a diverse group of small leucine-rich proteoglycans, enhanced the expression of cardioprotective genes and decreased ischemia/reperfusion-induced cardiomyocyte death via a TLR-4 dependent mechanism. Therefore, in the present study we aimed to test whether decorin, a small leucine-rich proteoglycan closely related to biglycan, could exert cardiocytoprotection and to reveal possible downstream signaling pathways. Methods: Primary cardiomyocytes isolated from neonatal and adult rat hearts were treated with 0 (Vehicle), 1, 3, 10, 30 and 100 nM decorin as 20 h pretreatment and maintained throughout simulated ischemia and reperfusion (SI/R). In separate experiments, to test the mechanism of decorin-induced cardio protection, 3 nM decorin was applied in combination with inhibitors of known survival pathways, that is, the NOS inhibitor L-NAME, the PKG inhibitor KT-5823 and the TLR-4 inhibitor TAK-242, respectively. mRNA expression changes were measured after SI/R injury. Results: Cell viability of both neonatal and adult cardiomyocytes was significantly decreased due to SI/R injury. Decorin at 1, 3 and 10 nM concentrations significantly increased the survival of both neonatal and adult myocytes after SI/R. At 3nM (the most pronounced protective concentration), it had no effect on apoptotic rate of neonatal cardiac myocytes. No one of the inhibitors of survival pathways (L-NAME, KT-5823, TAK-242) influenced the cardiocytoprotective effect of decorin. MYND-type containing 19 (Zmynd19) and eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1) were significantly upregulated due to the decorin treatment. In conclusion, this is the first demonstration that decorin exerts a direct cardiocytoprotective effect possibly independent of NO-cGMP-PKG and TLR-4 dependent survival signaling.

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l-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: a double-edged sword phenomenon

Cited by 13 publications

References 35 publications

NMR-Based Metabolomic Analysis of Sera in Mouse Models of CVB3-Induced Viral Myocarditis and Dilated Cardiomyopathy

NMR-Based Metabolomic Analysis of Sera in Mouse Models of CVB3-Induced Viral Myocarditis and Dilated Cardiomyopathy

Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk

Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury

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