Ethanol protects against lysophosphatidylcholine-induced uncoupling of cardiac cell pairs

Daleau, Pascal

doi:10.1007/s00424-002-0896-8

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…The exogenous lysoPC was also proven to induce myoischemia-like injury in in vitro study. As the increase of [Ca 2+ ]i would cause irreversible injury of cardiomyocytes including reduction of cell-to-cell coupling, abnormal rhythmic activity and malignant intra-cardiac reentry, preservation of the level of [Ca 2+ ]i within normal range is important for the normalization of cardiac function [2,13-15]. Therefore, a drug that can minimize the detrimental effects of lysoPC could attenuate cardiac dysfunction during myocardial ischemia.…”

Section: Discussionmentioning

confidence: 99%

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways

Chen

Hsu

Liou

et al. 2014

BMC Complement Altern Med

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BackgroundLysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes.MethodsCell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer. Cell apoptosis and necrosis were evaluated by the flow cytometry assay and Hoechst staining. Mitogen-Activated Protein Kinases (MAPKs), which included the ERK, JNK, and p38, and the apoptotic mechanisms including Bcl-2/Bax, caspase-3, caspase-9 and cytochrome c pathways were examined by Western blot analysis. The activation of MAPKs was examined by enzyme-linked immunosorbent assay.ResultsWe found that lysoPC induced death and apoptosis of H9c2 cells in a dose-dependent manner. Baicalein could prevent lysoPC-induced cell death, production of reactive oxygen species (ROS), and increase of intracellular calcium concentration in H9c2 cardiomyoctes. In addition, baicalein also inhibited lysoPC-induced apoptosis, with associated decreased pro-apoptotic Bax protein, increased anti-apoptotic Bcl-2 protein, resulting in an increase in the Bcl-2/Bax ratio. Finally, baicalein attenuated lysoPC-induced the expression of cytochrome c, casapase-3, casapase-9, and the phosphorylations of ERK1/2, JNK, and p38. LysoPC-induced ERK1/2, JNK, and p38 activations were inhibited by baicalein.ConclusionsBaicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways

Chen

Hsu

Liou

et al. 2014

BMC Complement Altern Med

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“…Ethanol has a number of reported actions that may be beneficial in countering the LPC effect: modifying ionic channel activities [6,27], decreasing Ca 2+ peaks during the depolarization [25], inhibiting protein kinases [23], or increasing membrane fluidity [4]. However, the opposite actions of LPC and alcohols have only been clearly demonstrated at the level of membranes.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously reported that in isolated heart cells, ethanol at physiologically tolerated concentrations could delay the deleterious effects of L-palmitoyl-LPC (Ca 2+ overload and increased membrane permeability) [9] and that in isolated heart cells, ethanol can counteract the gap junction uncoupling induced by LPC [6].…”

Section: Introductionmentioning

confidence: 99%

Cut-off phenomenon in the protective effect of alcohols against lysophosphatidylcholine-induced calcium overload

Bordeleau¹,

Gailis

Fournier³

et al. 2005

Pflugers Arch - Eur J Physiol

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We studied the effect of chain length on the protective effect of alcohols against lysophosphatidylcholine (LPC)-induced Ca2+ overload in neonatal rat cardiomyocytes. We previously found that ethanol retards Ca2+ elevation. Cells were loaded with the Ca2+-sensitive fluorophore fura-2, and changes in fluorescence were followed. The addition of 10 microM LPC increased Ca2+, which reached a plateau after an 8-10 min delay. The presence of 88 mM n-propanol, n-butanol, tert-butanol, or 2,2-dimethylpropanol significantly increased the delay by 94-213%. However, n-pentanol at 2 mM or 88 mM had no protective effect. Among n-alcohols, the increase in lag time was inversely proportional to the length of the carbon chain. Chain length, rather than molecular weight determines the effect, because 2,2-dimethylpropanol had a protective effect. The influence of alcohols on LPC micelle formation was estimated from the increase in octadecyl rhodamine B fluorescence; the increase by n-alcohols was directly proportional to chain length, indicating that micelle formation was not involved in the extension of lag time. The absence of the protective effect when the alcohol aliphatic chain exceeds four carbons suggests that the effect of ethanol may be mediated via a small lipophilic pocket on a protein, or to lateral pressure perturbation in the membrane.

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Lipid metabolites and their differential pro-arrhythmic profiles: of importance in the development of a new anti-arrhythmic pharmacology

et al. 2014

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Arrhythmias have been treated for a long time with drugs that mainly target the ionic pumps and channels. These anti-arrhythmic regimens per se introduce new arrhythmias, which can be detrimental to patients. Advances in development of novel pharmacology without introduction of iatrogenic arrhythmias are thus favorable for an effective treatment of arrhythmias. Electrophysiological stability of the heart has been shown to be closely associated with cardiac metabolism. The present effective anti-arrhythmic drugs such as beta-blockers and amiodarone have profound beneficial effects in regulating myocardial metabolism. Aiming at decreasing production of toxic metabolites or preventing accumulation of arrhythmogenic lipids perhaps is a good strategy to effectively control arrhythmias. Therefore, a better understanding of the pro-arrhythmic profiles of cardiac metabolites helps to explore a new generation of metabolically oriented anti-arrhythmic medications. In this review, we present several lipid metabolites and summarize their arrhythmogenic characteristics.

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Ethanol protects against lysophosphatidylcholine-induced uncoupling of cardiac cell pairs

Cited by 4 publications

References 40 publications

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways

Cut-off phenomenon in the protective effect of alcohols against lysophosphatidylcholine-induced calcium overload

Lipid metabolites and their differential pro-arrhythmic profiles: of importance in the development of a new anti-arrhythmic pharmacology

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