PFKFB2 inhibits ferroptosis in myocardial ischemia/reperfusion injury through AMPK activation.

Abstract

6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) is a key regulator of glycolytic enzyme. This study identified if PFKFB2 can regulate myocardial ferroptosis in ischemia/reperfusion (I/R) injury. Mice myocardial (I/R) injury and H9c2 cells oxygen-glucose deprivation/reperfusion (OGD/R) models were established. PFKFB2 expression was enhanced in I/R mice and OGD/R H9c2 cells. Overexpression of PFKFB2 improves heart function in I/R mice. Overexpression of PFKFB2 inhibits I/R and OGD/R-induced ferroptosis in mice and H9c2 cells. Mechanistically, overexpression of PFKFB2 activating the adenosine monophosphate activated protein kinase (AMPK). AMPK inhibitor compound C reverses effect of PFKFB2 overexpression in reducing ferroptosis under OGD/R treatment. In conclusion, PFKFB2 protects hearts against I/R-induced ferroptosis through activation of AMPK signaling pathway.