Curcumin reduces myocardial ischemia-reperfusion injury, by increasing endogenous HS levels and further modulating mA.

BACKGROUND

Our previous research shows that Curcumin (CUR) attenuates myocardial ischemia-reperfusion injury (MIRI) by reducing intracellular total RNA mA levels. However, the mechanism remains unknown.

METHODS

For ischemia-reperfusion (IR), H9c2 cells were cultured for 6 h in serum-free low-glycemic (1 g/L) medium and a gas environment without oxygen, and then cultured for 6 h in high-glycemic (4.5 g/L) medium supplemented with 10% FBS and a 21% oxygen environment. The effects of different concentrations of CUR (5, 10, and 20 µM) treatments on signaling molecules in conventionally cultured and IR-treated H9c2 cells were examined.

RESULTS

CUR treatment significantly up-regulated the HS levels, and the mRNA and protein expression of cystathionine γ-lyase (CSE), and down-regulated the mRNAs and proteins levels of thiosulfate sulfurtransferase (TST) and ethylmalonic encephalopathy 1 (ETHE1) in H9c2 cells conventionally cultured and subjected to IR. Exogenous HS supply (NaHS and GYY4137) significantly reduced intracellular total RNA mA levels, and the expression of RNA mA "writers" METTL3 and METTL14, and increased the expression of RNA mA "eraser" FTO in H9c2 cells conventionally cultured and subjected to IR. CSE knockdown counteracted the inhibitory effect of CUR treatment on ROS production, promotion on cell viability, and inhibition on apoptosis of H9c2 cells subjected to IR.

CONCLUSION

CUR attenuates MIRI by regulating the expression of HS level-regulating enzymes and increasing the endogenous HS levels. Increased HS levels could regulate the mA-related proteins expression and intracellular total RNA mA levels.