Ganoderic Acid A Protects Rat H9c2 Cardiomyocytes from Hypoxia-Induced Injury via Up-Regulating miR-182-5p

Abstract

Background/Aims: Ganoderic acid A (GAA) isolated from Ganoderma lucidum, shows various benefit activities, such as anti-tumor activity, anti-HIV activity and hepatoprotective activity. However, the potential effects of GAA on hypoxia-induced injury of cardiomyocytes are still unclear. In this study, we aimed to reveal the effects of GAA on hypoxic-induced H9c2 cell injury, as well as potential underlying molecular mechanisms. Methods: Rat H9c2 cardiomyocytes were cultured in hypoxia condition with different doses of GAA. Cell viability and apoptosis were detected by CCK-8 assay and flow cytometry, respectively. qRT-PCR was performed to assess the expression levels of microRNA-182-5p (miR-182-5p) and phosphatase and tensin homologue (PTEN). Cell transfection was conducted to change the expression levels of miR-182-5p and PTEN in H9c2 cells. Finally, protein levels of key factors involved in cell proliferation, cell apoptosis and PTEN/PI3K/AKT pathway were evaluated using western blotting. Results: Hypoxia treatment significantly induced H9c2 cell viability loss and apoptosis. GAA incubation remarkably protected H9c2 cells from hypoxia-induced viability loss, proliferation inhibition and apoptosis. In addition, GAA obviously enhanced the expression level of miR-182-5p in H9c2 cells. Suppression of miR-182-5p notably alleviated the protective effects of GAA on hypoxia-treated H9c2 cells. Furthermore, miR-182-5p negatively regulated the mRNA and protein levels of PTEN in H9c2 cells. GAA attenuated hypoxia-induced inactivation of PI3K/AKT pathway in H9c2 cells by up-regulating miR-182-5p and then down-regulating PTEN. Conclusion: GAA protected rat H9c2 cardiomyocytes from hypoxia-induced injury might via up-regulating miR-182-5p, down-regulating PTEN and then activating PI3K/AKT signaling pathway.

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

“…In accordance with the research basis, we probed the influences of GAA in hypoxia‐provoked impairment in PC12 cells. Our discoveries were similar with the above research from Zhang et al (). We found that GAA management distinctly expedited cell viability and migration and meanwhile restrained apoptosis in hypoxia‐impaired PC12 cells.…”

“…HYPO in figure indicated hypoxia disposition; * p < .05, ** p < .01, *** p < .001 of GAA in hypoxia-provoked impairment in PC12 cells. Our discoveries were similar with the above research from Zhang et al (2018a).…”

“…Other recent literature disclosed that GAA could assuage hypoxia‐provoked rat neural stem cells apoptosis, autophagy, and inflammation via mediation of PI3K/AKT and mTOR pathways (Chang & Kong, ). Outside of this, a momentous research from Zhang, Xiao, and Liu () revealed that GAA could protect H9c2 cells to resist hypoxia‐triggered impairment. In accordance with the research basis, we probed the influences of GAA in hypoxia‐provoked impairment in PC12 cells.…”

“…An interesting research discovered that miR‐153 inhibition could guard neurons against ischemia/reperfusion injury in an oxygen‐glucose deprivation and reoxygenation model through adjusting nuclear factor erythroid 2‐related factor 2/heme oxygenase 1 signaling (Ji et al, ). Further, in the existing research, we only looked up that GAA could protect rat H9c2 cardiomyocytes against hypoxia‐triggered injury through modulating miR‐182‐5p (Zhang, Xiao, & Liu, ), but the influences of miR‐153 in cerebral ischemia remain uninvestigated. Moreover, whether miR‐153 joins in the regulation of the functions of GAA in hypoxia‐impaired PC12 cells is still unclear.…”

Retracted: LncRNA‐LET relieves hypoxia‐induced injury in H9c2 cells through regulation of miR‐138

“…23 As compared to the cells exposed to normoxia, the viability of cells in hypoxia group was significantly declined (P < .01, Figure 1A). 23 As compared to the cells exposed to normoxia, the viability of cells in hypoxia group was significantly declined (P < .01, Figure 1A).…”