Downregulation of miR-122 attenuates hypoxia/reoxygenation (H/R)-induced myocardial cell apoptosis by upregulating GATA-4

It is proposed that myocardial cell apoptosis causes ventricular remodeling and heart failure. The aim of the present study was to determine the effects of rutaecarpine (Rut) on hypoxia–reoxygenation (H–R)-induced apoptosis in myocardial cell line H9c2, as well as the underlying mechanisms. Cultured H9c2 cells were exposed to hypoxia for 24 h, followed by 12 h reoxygenation. Rut (in concentrations of 0.1, 1, and 10 µmol/L) was added 1 h prior to H–R. Cell viability and lactate dehydrogenase were measured to evaluate the cell injuries. Apoptosis was evaluated by Hoechst 33258 staining and flow cytometry. NADPH oxidase activity was measured by assay kit; intracellular reactive oxygen species (ROS) generation was detected by 2′,7′-dichlorofluorescein diacetate; and Nox2, Nox4, and p47phox mRNA and protein expression were analyzed by real-time PCR and Western blotting, respectively. The results showed that H–R significantly decreased cell viability and increased the lactate dehydrogenase release, as well as the apoptotic rate, concomitantly with enhanced NADPH oxidase activity. H–R also upregulated mRNA and protein expressions of Nox2, Nox4, and p47phox and increased ROS production. Treatment with Rut markedly reversed these effects introduced by H–R. These results suggest that the protective effects of Rut against H–R-induced myocardial cell injury and apoptosis might, at least partly, be due to the inhibition of the NADPH oxidase – ROS pathway.

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Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03270-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

He Tai ◽

Xiao-lin Jiang ◽

Zhi-ming Lan ◽

Yue Li ◽

Liang Kong ◽

...

Keyword(s):

Mitochondrial Function ◽

Cell Apoptosis ◽

Mitochondrial Permeability Transition ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Abdominal Cavity ◽

Myocardial Cell ◽

Renal Ischemia ◽

Tanshinone Iia ◽

Obese Rats

Abstract Background Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Methods Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. After 24 h of reperfusion, the rats were anaesthetized, the blood were fetched from the abdominal aorta and kidney were fetched from abdominal cavity, then related indicators were examined. Results TIIA combined with CsA can alleviate the pathohistological injury and apoptosis induced by renal IR in myocardial cells. TIIA combined with CsA improved cardiac function after renal ischemia (30 min)-reperfusion (24 h) in obese rats. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes. The injury of mitochondrial dynamic function was assessed by decrease in dynamin-related protein 1 (Drp1), and increases in mitofusin1/2 (Mfn1/2), and mitochondrial biogenesis injury was assessed by decreases in PPARγ coactivator-1-α (PGC-1), nucleo respiratory factor1 (Nrf1), and transcription factor A of mitochondrial (TFam). Conclusion We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

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Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa154 ◽

2020 ◽

Author(s):

Kang Zhou ◽

Yan Xu ◽

Qiong Wang ◽

Lini Dong

Keyword(s):

Cell Viability ◽

Cell Apoptosis ◽

Myocardial Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Damage ◽

Protective Role ◽

Human Cardiomyocytes ◽

Hypoxia Reoxygenation

Abstract Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3ʹ-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

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