Antiarrhythmic effect of lithium in rats after myocardial infarction by activation of Nrf2/HO-1 signaling

Lee, Tsung Ming; Lin, Shinn Zong; Chang, Nen Chung

doi:10.1016/j.freeradbiomed.2014.08.022

Cited by 59 publications

(43 citation statements)

References 42 publications

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“…Notably, the mechanisms of action of some drugs against myocardial infarction injuries suggest an association between HO-1 induction and activation of transcription factor NF-E2-related factor 2 (Nrf2). Nrf-2 has been shown to regulate the bioactivities of many phase II detoxifying enzymes, including HO-1, including evidence that activation of Nrf 2/HO-1 signaling confers antiarrhythmic effects in rats after myocardial ischemia [15].…”

Section: Introductionmentioning

confidence: 99%

Ergosterol Attenuates LPS-Induced Myocardial Injury by Modulating Oxidative Stress and Apoptosis in Rats

Lin

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ergosterol (ER) is the primary sterol found in fungi and is named after the ergot fungus. A variety of pharmacological activities have been reported for ER, including antioxidative, anti-proliferative, and anti-inflammatory effects, although its role in sepsis remains unclear. Methods: The protective effect of ER on lipopolysaccharide (LPS)-induced sepsis myocardial injury was evaluated both in vivo and in vitro. Rats were pretreated with ER and then with LPS. Histopathology of heart tissues was first performed. Subsequently, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), creatine kinase MB fraction (CK-MB), and lactate dehydrogenase (LDH) in serum and heart tissues were assessed by enzyme-linked immunosorbent assay kits. Western blotting was further used to evaluate the expression of antioxidant proteins (HO-1 and cytochrome c) and apoptosis associated proteins (Bcl-2, Bax, cleaved-caspase-3, cleaved-caspase-9, and cleaved-PARP). In addition, the effects of ER on oxidative stress biomarkers and apoptosis proteins were also detected in LPS-treated H9C2 cells. Moreover, small interfering Nrf2 RNA was transfected to H9C2 cells to study the role of Nrf2 signaling in connection with the protective effects of ER. Results: Pretreatment with ER ameliorated the histopathological changes in heart tissue induced by LPS injection, increased SOD activity, and reduced MDA content, and CK-MB and LDH levels. Furthermore, ER restored the expression of Nrf-2 and HO-1 in rat hearts, attenuating apoptotic damage via up-regulation of Bcl-2 in combination with the inhibition of Bax, cytochrome c, cleaved-caspase-3 and 9, and PARP, as revealed by western blot. When Nrf2 was blocked by siRNA, the effects of ER on SOD and MDA activity, as well as the expression of the antioxidant proteins and apoptosis-associated proteins were abolished. Conclusions: We demonstrated that ER has a cardioprotective effect in LPS-induced sepsis model through modulation of the antioxidant activity and anti-apoptosis effects and this process might be regulated by Nrf2 signaling.

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Section: Introductionmentioning

confidence: 99%

Ergosterol Attenuates LPS-Induced Myocardial Injury by Modulating Oxidative Stress and Apoptosis in Rats

Lin

Wang

et al. 2018

Cell Physiol Biochem

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“…There are therefore clearly cell type-specific responses to resistin. Very recently, we have demonstrated that PI3K pathway is a signalling pathway involving NGF expression and post-infarction sympathetic innervation [20]. The effect of resistin on myocardial sympathetic activity remains unclear, and whether sitagliptin can attenuate NGF expression by directly regulating the expression and secretion of resistin is unknown.…”

Section: Introductionmentioning

confidence: 99%

Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats

2016

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SynopsisMyocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptintreated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein.

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“…5 The specific chemiluminescence signal was calculated after subtraction of background activity, and expressed as counts per minute per milligram weight (cpm/mg).…”

Section: Laboratory Measurementsmentioning

confidence: 99%

“…3 Reactive oxygen species (ROS) have a strong impact on ventricular remodeling after myocardial infarction (MI). 4, 5 Very recently, we demonstrated that oxidative stress is increased in the…”

mentioning

confidence: 99%

“…4, 5 During the chronic stage of MI, regional increase of sympathetic nerves was commonly observed at the remote zone. 6 A nerve sprouting, due to increased sympathetic reinnervation, has been shown to be an important contributing factor in the occurrence of ventricular arrhythmias and sudden cardiac death in the healing or healed stage of MI in both animals 7, 8 and humans.…”

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confidence: 99%

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Dipeptidyl Peptidase-4 Inhibition Attenuates Arrhythmias via a Protein Kinase A-Dependent Pathway in Infarcted Hearts

Lee

Chen

Chang

2015

Circ J

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Background:The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on arrhythmias remains unknown. The aim of this study was to investigate whether sitagliptin attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression, focusing on cyclic adenosine monophosphate (cAMP) downstream signaling such as protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). Methods and Results:Male Wistar rats were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after ligating the coronary artery. Post-infarction was associated with increased oxidative stress. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats compared with sham. Compared with the vehicle, infarcted rats treated with sitagliptin had significantly increased cAMP levels, decreased DPP-4 activity, oxidative stress, NGF levels and immunofluorescence-stained sympathetic hyperinnervation. Arrhythmic scores were significantly lower in the sitagliptin-treated infarcted rats than in vehicle. Ex vivo studies showed that sitagliptin increased the phosphorylated cAMP response element-binding protein (CREB), which can be reversed by H-89 (a PKA inhibitor), not brefeldin A (an Epac inhibitor). Heme oxygenase-1 (HO-1) expression was increased by a PKA agonist but not by an Epac agonist. HO-1 expression was attenuated in KG-501 (a CREB inhibitor)-treated infarcted rats in the presence of a PKA agonist. Conclusions:Sitagliptin protects ventricular arrhythmias by attenuating NGF-induced sympathetic innervation via upregulation of HO-1 expression in a cAMP/PKA/CREB-dependent antioxidant pathway in non-diabetic infarcted rats. (Circ J 2015; 79: 2461-2470

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Antiarrhythmic effect of lithium in rats after myocardial infarction by activation of Nrf2/HO-1 signaling

Cited by 59 publications

References 42 publications

Ergosterol Attenuates LPS-Induced Myocardial Injury by Modulating Oxidative Stress and Apoptosis in Rats

Ergosterol Attenuates LPS-Induced Myocardial Injury by Modulating Oxidative Stress and Apoptosis in Rats

Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats

Dipeptidyl Peptidase-4 Inhibition Attenuates Arrhythmias via a Protein Kinase A-Dependent Pathway in Infarcted Hearts

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