{Reference Type}: Journal Article
{Title}: Circ_0004771 Promotes Hypoxia/Reoxygenation Induced Cardiomyocyte Injury via Activation of Mitogen-Activated Protein Kinase Signaling Pathway.
{Author}: Yu CJ;Xia F;Ruan L;Hu SP;Zhu WJ;Yang K;
{Journal}: Int Heart J
{Volume}: 64
{Issue}: 6
{Year}: 2023 Nov 30
{Factor}: 1.823
{DOI}: 10.1536/ihj.23-333
{Abstract}: This study aimed to observe the mechanism and effect of circ_0004771 on cardiomyocyte injury in acute myocardial infarction (AMI). The differences in circ_0004771 expression in the blood of AMI patients and healthy volunteers were observed by Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction. AMI cell models were constructed by hypoxia/reoxygenation (H/R)-induced injury in human cardiomyocytes (AC16 cells). The changes of circ_0004771 expression in AMI cells were observed. After transfection with the knockdown or overexpression of circ_0004771 vector in AMI cells, Cell Counting Kit-8 (CCK-8) assay and propidium iodide/FITC-Annexin V staining were performed to detect cell proliferation and apoptosis levels, extracellular lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) activity. Expression levels of Mitogen-activated protein kinase (MAPK) signaling pathway-related proteins (p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2), and endoplasmic reticulum (ER) stress proteins (GRP78 and CHOP-1) were observed in each group of cells by western blot method. The expression level of circ_0004771 was significantly reduced in both clinical samples and cells of AMI. When circ_0004771 was knocked down in AMI cells, it resulted in a decrease in cell proliferation level and significant increase in apoptosis level. The inhibition of circ_0004771 expression caused leakage of LDH in AMI cells, accumulation of intracellular MDA, and inhibition of SOD activity. In addition, the knockdown of circ_0004771 significantly increased the levels of p-MEK1/2, p-ERK1/2, GRP78, and CHOP-1 in H/R-induced AC16 cells. However, the overexpression of circ_0004771 resulted in the opposite result as when circ_0004771 was knocked down. A low level of circ_0004771 in AMI activates the MAPK signaling pathway in cardiomyocytes as well as encourages intracellular oxidative stress and ER stress, thereby inhibiting cell proliferation and promoting apoptosis.