Overexpression of microRNA-146 protects against oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis by inhibiting the NF-κB/TNF-α signaling pathway

Abstract

MicroRNA (miR) has been reported to be associated with ischemia and reperfusion (I/R) and cell apoptosis. Suppression of cell apoptosis may reduce the irreversible damage induced by reperfusion. The aims of the current study were to explore the cytoprotective effects of miR-146 against oxygen-glucose deprivation/recovery (OGD/R)-induced injury in H9c2 rat myocardial cells, as well as the underlying mechanisms. Following stimulation with OGD/R, the cells were transfected with miR-146 mimics or negative controls. The levels of miR-146 were analyzed by reverse transcription-quantitative polymerase chain reaction. Thereafter, cell viability and cell apoptosis were analyzed by MTT assay and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling assay, respectively. In addition, the levels of tumor necrosis factor (TNF)-α were determined by ELISA and the levels of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2 and phosphorylated (p)-nuclear factor (NF)-κB were measured by western blotting. The results demonstrated that overexpression of miR-146 significantly increased cell viability and decreased apoptosis (P<0.05). It was observed that overexpression of miR-146 statistically reduced the levels of Bax, TNF-α and p-NF-κB but markedly upregulated the levels of Bcl-2 (P<0.05). These results indicate that overexpression of miR-146 may protect against OGD/R-induced cardiomyocyte apoptosis. Overexpression of miR-146 may alleviate the irreversible injury associated with reperfusion and the effects may be achieved by inhibiting the NF-κB/TNF-α signaling pathway.

Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway

“…Studies have shown that NF-κB signaling was related to apoptosis. That is to say, high activity of NF-κB signaling could cause anti-apoptosis in cancer cells [ 52 – 54 ]. Therefore, suppression of NF-κB signaling was probably responsible for Andro-induced apoptosis in MCF-7, which could also inhibit COX-2 expression.…”

Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model

“…The present study demonstrated that BAC induction of DED provoked NF-κB activation, which was markedly suppressed by topical CsA, consistent with decreased expression of inflammatory mediators. We suggest that CsA suppression of NF-κB signalling may down-regulate expression of inflammatory molecules, including cytokines such as IL-1β [38–40], TNF-α [40, 41] and IL-6 [40, 42, 43], and chemokines [44–46] such as ICAM-1 and VCAM-1.…”

MicroRNAs as Potential Pharmaco-Targets in Ischemia-Reperfusion Injury Compounded by Diabetes

“…This synergistic effect might be due to the fact that each of the aforementioned miRNAs inhibits p38-caspase3-induced apoptosis via different mechanisms [98,99] (Figure 4). For instance, miR-21 attenuates cardiomyocyte injury via regulating the programmed cell death 4 (PDCD4) and AKT pathway, whereas miR-146a exerts its protective antiapoptotic effects through modulating interleukin-1 receptor-associated kinase1 (IRAK1), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and the NF-κB/TNF-α pathways [100,101,102]. This finding opens the window to a potential synergistic effect of multiple miRNAs and their impact on disease prevention or progression [57].…”