Dataset Information

Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling.

ABSTRACT: BACKGROUND:Acute myocardial infarction (AMI) is the leading cause of death globally and has thus placed a heavy burden on healthcare. Tanshinone IIA (TSA) is a major active compound, extracted from Salvia miltiorrhiza Bunge, that possesses various pharmacological activities. The aim of the present study was to investigate the role of TSA in AMI and its underlying mechanism of action. RESULTS:We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression. CONCLUSION:TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

SUBMITTER: Chen L

PROVIDER: S-EPMC7099794 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling.

Chen Liye L Wei Lili L Yu Qiongyang Q Shi Haozhe H Liu George G

BMC molecular and cell biology 20200327 1

<h4>Background</h4>Acute myocardial infarction (AMI) is the leading cause of death globally and has thus placed a heavy burden on healthcare. Tanshinone IIA (TSA) is a major active compound, extracted from Salvia miltiorrhiza Bunge, that possesses various pharmacological activities. The aim of the present study was to investigate the role of TSA in AMI and its underlying mechanism of action.<h4>Results</h4>We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS ...[more]

PMID: 32220226

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Project description:ObjectivesTo explore the effects of miR-16-5p and PTPN4 on the apoptosis and autophagy of AC16 cardiomyocytes after hypoxia/reoxygenation treatment.MethodsAC16 cells were divided into the control group (NC), hypoxia/reoxygenation group (H/R), knockdown miR-16-5p negative control group (NC inhibitor), knockdown miR-16-5p group (miR-16-5p inhibitor), overexpression miR-16-5p negative control group (NC mimics), overexpression miR-16-5p group (miR-16-5p mimics), silent PTPN4 negative control group (sh-NC), silent PTPN4 group (sh-PTPN4), and silent PTPN4 + knockdown miR-16-5p group (sh-PTPN4 + miR-16-5p inhibitor). Real-time fluorescent quantitative PCR (RT-qPCR) and western blotting (WB) were used to measure the expression level of miR-16-3p, miR-16-5p, protein tyrosine phosphatase nonreceptor type 4 (PTPN4), and autophagy-related proteins (beclin-1, LC3 II/I, and P26) in AC16 cells. The apoptosis level of AC16 cells in each group was measured by flow cytometry and TUNEL. The dual-luciferase reporter gene experiment was also used to verify the targeting relationship between miR-16-5p and PTPN4.ResultsAfter H/R treatment, the levels of myocardial injury markers including LDH and CK-MB in AC16 cells were increased significantly (P < 0.05), and the levels of cell apoptosis and autophagy also increased significantly (P < 0.05). The level of miR-16-3p in AC16 cells did not change significantly after H/R treatment, whereas the level of miR-16-5p was increased significantly (P < 0.05). After miR-16-5p was knocked down, the levels of LDH and CK-MB in AC16 cells treated with H/R were significantly reduced (P < 0.05), and the rates of cell apoptosis and autophagy were also significantly reduced (P < 0.05). miR-16-5p negatively regulated the expression level of PTPN4 protein in AC16 cells (P < 0.05), and the dual-luciferase reporter gene experiment confirmed that PTPN4 was the downstream target of miR-16-5p. Silencing of PTPN4 significantly increased the damage of AC16 cells induced by H/R treatment (P < 0.05), but simultaneously inhibiting the expression of PTPN4 and miR-16-5p reversed the protective effect of miR-16-5p knockdown on AC16 cells (P < 0.05).ConclusionsThe expression of miR-16-5p is upregulated in AC16 cells after H/R treatment and the knockdown which can protect AC16 cells from H/R-induced cell damage that may be due to its regulation on the expression of PTPN4.

Project description:Background Few reports have addressed the mechanism by which microRNA miR-10b-5p regulates post-myocardial infarction (post-MI) cardiomyocyte apoptosis under hypoxic conditions. Methods and Results C57BL/6 mice underwent surgical ligation of the left anterior descending artery to create an MI or ischemia/reperfusion animal model. The expression of miR-10b-5p, PTEN (phosphatase and tensin homolog), and HIF-1? (hypoxia-inducible factor 1?) was detected in infarct border zone tissues at various time points. After precordial injections of the negative control or miR-10b-5p, overexpression lentiviruses were made in the areas surrounding the MI sites at 1 week, and myocardial infarct size, cardiac function, and cardiomyocyte apoptosis were examined. A miR-10b-5p mimic was transfected into primary mouse cardiomyocytes to analyze its effects on cardiomyocyte apoptosis and PTEN expression. Meanwhile, PTEN as a target of miR-10b-5p was verified via luciferase reporter gene assays. Cotransfection of miR-10b-5 and PTEN verified the relationship between miR-10b-5 and PTEN. Under hypoxic stress, the expression of HIF-1? and miR-10b-5p was examined. The results showed that miR-10b-5p expression was markedly reduced in the infarct border zone. Overexpression of miR-10b-5p in the murine model of MI significantly reduced MI size, improved cardiac function, and inhibited apoptosis. Overexpression of miR-10b-5p in vitro antagonized hypoxia-induced cardiomyocyte apoptosis and specifically inhibited the expression of the apoptosis-related gene PTEN, but overexpression of PTEN weakened these effects. We also found that hypoxia-induced accumulation of HIF-1? resulted in decreased expression of miR-10b-5p. Interfering with the activation of the HIF-1? signaling pathway promoted Pri-miR-10b and miR-10b-5p expression and inhibited PTEN expression. Conclusions MicroRNA miR-10b-5p antagonizes hypoxia-induced cardiomyocyte apoptosis, indicating that miR-10b-5p may serve as a potential future clinical target for the treatment of MI.

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Dataset Information

Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling.

Publications

Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling.

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