Propofol synergizes with circAPBB2 to protect against hypoxia/reoxygenation-induced oxidative stress, inflammation, and apoptosis of human cardiomyocytes

Myocardial injury is the main manifestation of cardiovascular diseases, and previous studies have shown that propofol (PPF) regulates myocardial injury. However, the mechanism of PPF in regulating myocardial injury remains to be further explored. This work aims to analyze the effects of PPF on human cardiomyocyte injury and the underlying mechanism.

PPF synergized with circAPBB2 to protect AC16 cells against H/R-induced oxidative stress, inflammation and apoptosis through the miR-18a-5p/DUSP14 pathway.

The regulatory and functional role of PPF and circAPBB2 in human cardiomyocyte injury were analyzed using an in vitro hypoxia/reoxygenation (H/R) cell model, which was established by treating human cardiomyocytes (AC16 cells) with H/R. The study evaluated AC16 cell injury by analyzing cytotoxicity, oxidative stress, inflammation and apoptosis of H/R-induced AC16 cells. Quantitative real-time polymerase chain reaction was performed to detect circAPBB2, miR-18a-5p and dual specificity phosphatase 14 (DUSP14) expression. Protein expression was analyzed by Western blot analysis assay. Dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay were performed to identify the associations among circAPBB2, miR-18a-5p and DUSP14. Cytotoxicity was investigated by cell counting kit-8 assay and lactate dehydrogenase activity detection kit. Oxidative stress was evaluated by cellular reactive oxygen species assay kit and superoxide dismutase activity assay kit. The production of tumor necrosis factor-α and interleukin-1β was evaluated by enzyme-linked immunosorbent assays.

The expression of circAPBB2 and DUSP14 was significantly decreased, while miR-18a-5p was increased in H/R-induced AC16 cells when compared with controls. H/R treatment-induced cytotoxicity, oxidative stress, inflammation and cell apoptosis were attenuated after circAPBB2 overexpression or PPF treatment, whereas these effects were restored by increasing miR-18a-5p expression. PPF treatment improved the inhibitory effect of ectopic circAPBB2 expression on H/R-induced cell injury. MiR-18a-5p silencing ameliorated H/R-induced AC16 damage by interacting with DUSP14. Mechanically, circAPBB2 acted as a miR-18a-5p sponge, and miR-18a-5p targeted DUSP14 in AC16 cells.