Transcriptional activation of ENPP2 by FoxO4 protects cardiomyocytes from doxorubicin‑induced toxicity

• DOI: 10.3892/mmr.2021.12307
• Publication Date: 2021-07-20T12:28:20Z
• Authors: Ling He; Yuting Yang; Juan Chen; Pengtao Zou; Juxiang Li
• Keywords: Viability assay

It has been shown that ferroptosis is involved in doxorubicin (DOX)‑induced cardiotoxicity and ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) can protect cardiomyocytes from ferroptosis. Thus, the present study aimed to investigate whether ENPP2 could DOX‑induced injury by inhibiting H9c2 were exposed various concentrations (0.625, 1.25, 2.5, 5 or 10 <em>µ</em>M) of DOX for different time periods. Cell viability expression determined. ENPP2‑overexpressing cells treated with subsequently cell viability, oxidative stress, autophagy measured using corresponding assays (MTT assay, commercial kits western blot analysis). Dual‑luciferase reporter chromatin immunoprecipitation assays, as well bioinformatics analysis, applied detect interaction between FoxO4. Following FoxO4 overexpression cells, aforementioned cellular processes assessed. The results indicated was downregulated following treatment DOX. also led decreased reduced elevated which notably reversed overexpression. In addition, bound promoter, resulting inhibition its expression. further experiments conducted analysis revealed partially inhibited effects on cells. conclusion, data transcriptionally regulated toxicity Therefore, specific approaches targeting FoxO4/ENPP2 axis may provide potential therapies alleviating cardiotoxicity.