Argon inhibits reactive oxygen species oxidative stress via the miR-21-mediated PDCD4/PTEN pathway to prevent myocardial ischemia/reperfusion injury

Abstract

The objective of this study was to explore the effect of argon preconditioning on myocardial ischemia reperfusion (MI/R) injury and its mechanism. Cardiomyocytes H2C9 were pre-treated with 50% argon, and a cell model of oxygen-glucose deprivation (OGD) was established. CCK-8 and cytotoxicity detection kits were used to detect cell viability and lactate dehydrogenase (LDH) release. The miR-21 expression was detected using quantitative real-time polymerase chain reaction. Western blot analysis was performed to detect the expression of programmed cell death protein 4 (PDCD4) and homologous phosphatase and tensin homolog (PTEN) proteins. The levels of inflammatory factors (IL-1β, IL-6, and IL-8) and oxidative stress factors (reactive oxygen species ROS], malondialdehyde [MDA], and superoxide dismutase [SOD]) were measured using an enzyme-linked immunosorbent assay. The effect of argon on cell apoptosis was detected using flow cytometry. Argon increased the proliferation of cardiomyocytes induced by OGD, decreased the release of LDH in cell culture medium, increased miR-21 expression in cells, decreased the expression of miR-21 target proteins PDCD4 and PTEN, decreased the levels of inflammatory factors , and interleukin-8 ) and oxidative stress factors (ROS and MDA), increased the SOD content, and decreased the cell apoptosis rate. Our results suggest that argon preconditioning inhibited the PDCD4/PTEN pathway via miR-21, thereby inhibiting ROS oxidative stress and preventing MI/R injury.

The mir-21 Inhibition Enhanced HUVEC Cellular Viability during Hypoxia-Reoxygenation Injury by Regulating PDCD4

“…It has been established that PDCD4 is crucial in regulating oxidized low-density lipoprotein (ox-LDL) metabolism, foam cell formation, coronary atherosclerosis, stress, and ischemia/reperfusion-induced cellular injuries [10][11][12]24]. From our luciferase analysis experiment results, from the TargetScan database, and also from other studies, it was confirmed that PDCD4 is the direct target protein of miR-21 [20,24,25].…”

“…It has been established that PDCD4 is crucial in regulating oxidized low-density lipoprotein (ox-LDL) metabolism, foam cell formation, coronary atherosclerosis, stress, and ischemia/reperfusion-induced cellular injuries [10][11][12]24]. From our luciferase analysis experiment results, from the TargetScan database, and also from other studies, it was confirmed that PDCD4 is the direct target protein of miR-21 [20,24,25]. The present study detected expressions of mir-21 in HR-exposed HUVECs which were highly upregulated as compared with the control group, but there were no significant effects noted between NC and HR groups.…”

A Small‐Molecule Probe with a Dual Function of miRNA Inhibition and Target identification

“…As AGO2 play pivotal roles in miRNA-mediated gene silencing, targeting AGO2 by 1 a and 1 b should rescue the Chemistry-A European Journal protein expressions of target mRNAs. It has been reported that miR-21 could target PTEN and PDCD4, [15] miR-25 could regulate BIM, [16] BCLÀ W and SRF were the targets of miR-122 [17] and miR-133a, [18] respectively. Then, protein expression levels of these genes were investigated after cells were treated with 10 μM 1 a and 1 b for 48 h. Compared to DMSO control, 1 a and 1 b led to significant increase in the protein levels (Figure 5), demonstrating the potential of 1 a and 1 b in regulating downstream targets of endogenous miRNAs.…”

Long non-coding RNA MEG3 promotes tumor necrosis factor-alpha induced oxidative stress and apoptosis in interstitial cells of cajal via targeting the microRNA-21 /I-kappa-B-kinase beta axis

“…A study by Zhou W et al proved that miR-21 could inhibit periodontitis by downregulating inflammation [ 52 ]. A study by Qi H et al reported miR-21 protects cardiomyocytes from ROS oxidative stress [ 53 ]. Another study by Li H et al indicated that the regulation of miR-21-5p suppresses hypoxia/reoxygenation injury-induced apoptosis of type II alveolar epithelial cells [ 54 ].…”