scholarly journals Schisandrol A Attenuates Myocardial Ischemia/Reperfusion-Induced Myocardial Apoptosis through Upregulation of 14-3-3θ

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Shuaishuai Gong ◽  
Jincheng Liu ◽  
Shiyao Wan ◽  
Weiwei Yang ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Functional Protein ◽  
Myocardial Apoptosis ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms ◽  
Stress Damage

Schisandrol A (SA), one of the most abundant bioactive lignans extracted from the Schisandra chinensis (Turcz.) Baill., has multiple pharmacological properties. However, the underlying mechanisms of SA in protection against myocardial ischemia/reperfusion (MI/R) injury remain obscure. The present experiment was performed to explore the cardioprotective effects of SA in MI/R injury and hypoxia/reoxygenation- (H/R-) induced cardiomyocyte injury and clarify the potential underlying mechanisms. SA treatment significantly improved MI/R injury as reflected by reduced myocardium infarct size, attenuated histological features, and ameliorated biochemical indicators. In the meantime, SA could profoundly ameliorate oxidative stress damage as evidenced by the higher glutathione peroxidase (GSH-Px) as well as lower malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, SA alleviated myocardial apoptosis as evidenced by a striking reduction of cleaved caspase-3 expression and increase of Bcl-2/Bax ratio. Further experiments demonstrated that SA had certain binding capability to the key functional protein 14-3-3θ. Mechanistically, SA prevented myocardial apoptosis through upregulating 14-3-3θ expression. Interestingly, siRNA against 14-3-3θ could promote apoptosis of cardiomyocytes, and H/R injury after knockdown of 14-3-3θ could further aggravate apoptosis, while overexpression of 14-3-3θ could significantly reduce apoptosis induced by H/R injury. Further, 14-3-3θ siRNA markedly weakened the antiapoptotic role of SA. Our results demonstrated that SA could exert apparent cardioprotection against MI/R injury and H/R injury, and potential mechanisms might be associated with inhibition of cardiomyocyte apoptosis at least partially through upregulation of 14-3-3θ.

scholarly journals The expression and role of β3AR protein in myocardial ischemia/reperfusion in rats

2021 ◽  
Author(s):  
Zi-Long Wang ◽  
Xiao-Chen Sun ◽  
Rong Luo ◽  
Dong-Ye Li ◽  
Hao-Chen Xuan
Keyword(s):  
Myocardial Ischemia ◽  
Protein Expression ◽  
Caspase 3 ◽  
Sham Group ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Sd Rats ◽  
Group I ◽  
Myocardial Ischemia Reperfusion

IntroductionTo explore serum norepinephrine (NE) concentration and β3-adrenoceptor (β3AR) protein expression at different times during myocardial ischemia/reperfusion (I/R) and examine the role of β3AR in I/R.Material and methods28 Sprague-Dawley (SD) rats were randomly divided into one sham group and six I/R groups. The rats in the I/R groups were subjected to ischemia for 45 minutes. After reperfusion, the serum NE concentration and the β3AR protein expression in the myocardial tissue of the left ventricular injury region were detected. Another 18 SD rats were randomly divided into a sham group, I/R groups, and I/R + BRL37344 group.ResultsCompared with the sham group, the serum NE concentration of rats in the I/R groups significantly increased at 6 hours (P < 0.001). The serum NE concentration and myocardial β3AR protein expression were both highest at 72 hours. Compared with the sham group, the expressions of the pro-apoptotic proteins Bax and cleaved caspase-3 after I/R were significantly increased (P < 0.01, P < 0.001, respectively), and the expression of anti-apoptotic protein Bcl-2 was significantly decreased (P < 0.01). Compared with I/R groups, the expressions of Bax and cleaved caspase-3 in the I/R + BRL37344 group were significantly decreased (P < 0.05, P < 0.01, respectively).ConclusionsWith the prolongation of myocardial I/R in rats, serum NE concentration and β3AR protein expression showed a significant increase trend and reached a peak at 72 hours. Specific β3AR agonist BRL37344 can reduce myocardial I/R injury in vivo in rats, alleviate apoptosis, reduce infarct size, and improve cardiac function.

Abstract 11928: Cardiospecific Overexpression of Carnosine Synthase Attenuates Myocardial Ischemia Reperfusion Injury

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shahid Baba ◽  
Deqing zhang ◽  
David Hoetker ◽  
Yiru Guo ◽  
Aruni Bhatnagar
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Membrane Lipids ◽  
Ischemia Reperfusion ◽  
Glycolytic Activity ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms

Even though myocardial ischemia/reperfusion (I/R) remains the leading cause of death, the underlying mechanisms remain incompletely understood. Increased formation of reactive carbonyl has been shown to be a common biochemical feature of I/R injury. These carbonyls are generated from the oxidation of proteins and membrane lipids. Reactive carbonyls such as methylglyoxal are generated from increased glycolytic activity during ischemia. Previous work in our lab has shown that the endogenous dipeptide carnosine (β-alanine-histidine) quenches both protein and lipid derived carbonyls. It can also buffer changes in intracellular pH and chelate metals that catalyze ROS production. In the heart, carnosine is synthesized by the ATP grasp enzyme (ATPGD1). Hence, we examined whether overexpression of ATPGD1 could increase carnosine synthesis in the heart and attenuate I/R injury. To overexpress ATPGD1, we generated mice in which the expression of the transgene was driven by cardiospecific α-MHC promoter. Two different ATPGD1Tg mouse lines were generated, which showed 10-15 fold higher abundance of ATPGD1 protein in the heart compared with their wild-type (WT) littermates. Cardiac levels of the histidyl dipeptides anserine and carnosine were approximately 100 fold higher in the ATPGD1Tg than WT mice hearts (WT: anserine 1.8±0.3 pmoles/mg protein, carnosine 6±1 pmoles/mg protein; ATPGD1-Tg: anserine 114±15 pmoles/mg protein, carnosine 615±44 pmoles/mg protein). No changes in the levels of these dipeptides were observed in other tissues of the ATPGD1Tg mice. Echocardiographic analysis showed that ATPGD1 overexpression did not affect cardiac function. When subjected to 30 min of coronary occlusion followed by 24 h of reperfusion, the infarct size was significantly lower in ATPGD1Tg than WT mice. Infarct size as the area of risk of left ventricle was 59±3.02% in WT mice and 38±2.73% in the ATPGD1-Tg mice (p<0.05 vs WT; n=7-8), indicating that increasing carnosine levels attenuates myocardial I/R injury. These findings reveal a novel cardioprotective role of endogenous histidyl dipeptides in decreasing I/R injury and suggest that treatment with such peptides may be a potential therapy for decreasing myocardial I/R injury and its progression of heart failure.

scholarly journals Taxifolin protects rat against myocardial ischemia/reperfusion injury by modulating the mitochondrial apoptosis pathway

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6383 ◽  
Author(s):  
Zhenqiu Tang ◽  
Chunjuan Yang ◽  
Baoyan Zuo ◽  
Yanan Zhang ◽  
Gaosong Wu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Myocardial Apoptosis ◽  
Cyt C ◽  
Myocardial Ischemia Reperfusion

Background Taxifolin (TAX), is an active flavonoid, that plays an underlying protective role on the cardiovascular system. This study aimed to evaluate its effect and potential mechanisms on myocardial ischemia/reperfusion (I/R) injury. Methods Healthy rat heart was subjected to I/R using the Langendorff apparatus. Hemodynamic parameters, including heart rate, left ventricular developed pressure (LVDP), maximum/minimum rate of the left ventricular pressure rise (+dp/dtmax and −dp/dtmin) and rate pressure product (RPP) were recorded during the perfusion. Histopathological examination of left ventricular was measured by hematoxylin-eosin (H&E) staining. Creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities in the effluent perfusion, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the tissue were assayed. Apoptosis related proteins, such as B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), and cytochrome c (Cyt-c) were also assayed by ELISA. Western blot was employed to determine apoptosis-executive proteins, including caspase 3 and 9. Transferase-mediated dUTP-X nick end labeling assay was performed to evaluate the effect TAX on myocardial apoptosis. Results Taxifolin significantly improved the ventricular functional recovery, as evident by the increase in LVDP, +dp/dtmax, −dp/dtmin and RPP, the levels of SOD, GSH-PX were also increased, but those of LDH, CK-MB, and MDA were decreased. Furthermore, TAX up-regulated the Bcl-2 protein level but down-regulated the levels of Bax, Cyt-c, caspase 3 and 9 protein, thereby inhibits the myocardial apoptosis. Discussion Taxifolin treatment remarkably improved the cardiac function, regulated oxidative stress and attenuated apoptosis. Hence, TAX has a cardioprotective effect against I/R injury by modulating mitochondrial apoptosis pathway.

scholarly journals Hydroxytyrosol Protects against Myocardial Ischemia/Reperfusion Injury through a PI3K/Akt-Dependent Mechanism

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-hao Pei ◽  
Jiao Chen ◽  
Liang Xie ◽  
Xiao-min Cai ◽  
Run-Hua Yang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Systolic Function ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Mechanistic Study ◽  
Myocardial Infarct Size ◽  
Myocardial Apoptosis ◽  
Group I ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Objective. To investigate the effects and mechanisms of hydroxytyrosol (HT) during the pathogenesis of myocardial ischemia reperfusion (I/R) in rat hearts.Methods. The rats were randomized into five groups: sham group, I/R group, HT+I/R group, HT+LY294002+I/R group, and LY+I/R group. Myocardial infarct size, markers of oxidative stress, extent of myocardial apoptosis, echocardiographically assessed cardiac function, and expression of Akt and GSK 3βwere measured in each group.Results. Prereperfusion administration of HT was associated with a significantly smaller area of myocardial infarction and remarkably decreased level of myocardial apoptosis and necrosis, as evidenced by a lower apoptotic index, reduced cleaved caspase-3, and the serum activities of lactate dehydrogenase and creatinine kinase MB. Moreover, HT also attenuated the impairment of cardiac systolic function. However, cotreatment with LY294002 and HT completely abolished the above cardioprotective effects of HT. A subsequent mechanistic study revealed that the cardioprotective effects of HT during the process of I/R of the myocardium were dependent on the activation of the Akt/GSK3βpathway.Conclusion. Pretreatment with HT may have antiapoptotic and cardioprotective effects against myocardial I/R injury, and these effects seem to be related to the activation of the Akt/GSK3βpathway in the myocardium.

Interleukin 35 protects cardiomyocytes following ischemia/reperfusion-induced apoptosis via activation of mitochondrial STAT3

2021 ◽  
Author(s):  
Fengyun Zhou ◽  
Ting Feng ◽  
Xiangqi Lu ◽  
Huicheng Wang ◽  
Yangping Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Cytochrome C Release ◽  
Neonatal Cardiomyocytes ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Abstract Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

MicroRNA-330-5p inhibits NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury by targeting TIM3

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Zuo ◽  
R Tian ◽  
Q Chen ◽  
L Wang ◽  
Q Gu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of human death. Nod-like receptor protein-3 (NLRP3) inflammasome signaling pathway involved in the pathogenesis of MIRI. However, the upstream regulating mechanisms of NLRP3 at molecular level remains unknown. Purpose This study investigated the role of microRNA330-5p (miR-330-5p) in NLRP3 inflammasome-mediated MIRI and the associated mechanism. Methods Mice underwent 45 min occlusion of the left anterior descending coronary artery followed by different times of reperfusion. Myocardial miR-330-5p expression was examined by quantitative polymerase chain reaction (PCR), and miR-330-5p antagomir and agomir were used to regulate miR-330-5p expression. To evaluate the role of miR-330-5p in MIRI, Evans Blue (EB)/2, 3, 5-triphenyltetrazolium chloride (TTC) staining, echocardiography, and immunoblotting were used to assess infarct volume, cardiac function, and NLRP3 inflammasome activation, respectively. Further, in vitro myocardial ischemia-reperfusion model was established in cardiomyocytes (H9C2 cell line). A luciferase binding assay was used to examine whether miR-330-5p directly bound to T-cell immunoglobulin domain and mucin domain-containing molecule-3 (TIM3). Finally, the role of miR-330-5p/TIM3 axis in regulating apoptosis and NLRP3 inflammasome formation were evaluated using flow cytometry assay and immunofluorescence staining. Results Compared to the model group, inhibiting miR-330-5p significantly aggravated MIRI resulting in increased infarct volume (58.09±6.39% vs. 37.82±8.86%, P&lt;0.01) and more severe cardiac dysfunction (left ventricular ejection fraction [LVEF] 12.77%±6.07% vs. 27.44%±4.47%, P&lt;0.01; left ventricular end-diastolic volume [LVEDV] 147.18±25.82 vs. 101.31±33.20, P&lt;0.05; left ventricular end-systolic volume [LVESV] 129.11±30.17 vs. 74.29±28.54, P&lt;0.05). Moreover, inhibiting miR-330-5p significantly increased the levels of NLRP3 inflammasome related proteins including caspase-1 (0.80±0.083 vs. 0.60±0.062, P&lt;0.05), interleukin (IL)-1β (0.87±0.053 vs. 0.79±0.083, P&lt;0.05), IL-18 (0.52±0.063 vs. 0.49±0.098, P&lt;0.05) and tissue necrosis factor (TNF)-α (1.47±0.17 vs. 1.03±0.11, P&lt;0.05). Furthermore, TIM3 was confirmed as a potential target of miR-330-5p. As predicted, suppression of TIM3 by small interfering RNA (siRNA) ameliorated the anti-miR-330-5p-mediated apoptosis of cardiomyocytes and activation of NLRP3 inflammasome signaling pathway (Figure 1). Conclusion Overall, our study indicated that miR-330-5p/TIM3 axis involved in the regulating mechanism of NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China Grants

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