Curcumin inhibits autophagy and apoptosis in hypoxia/reoxygenation-induced myocytes

Abstract

Abstract. Primary percutaneous coronary intervention, or thombolytic therapy, provides effective myocardial blood reconstruction in patients with acute myocardial infarction to reduce acute myocardial ischemic injury. However, reperfusion can itself induce cardiomyocyte death, termed myocardial reperfusion injury (I/R). Hypoxia/reoxygenation (H/R) induces apoptosis and excessive autophagy among cardiomyocytes, leading to cell death. The present study investigated the effect of curcumin, a natural extract from Curcuma longa, on these two cellular processes in H9c2 myocytes. The levels of cellular apoptosis and autophagy were found to be upregulated in the H9c2 myocytes during H/R and were correlated with a reduced rate of cell survival. However, curcumin significantly suppressed the levels of H/R-induced apoptosis (expression of annexin V) and autophagy (LC3B-II/LC3B-I ratio) in the H9c2 myocytes and promoted cell survival. Additionally, the expression of B-cell lymphoma 2 (Bcl-2) was significantly downregulated and the expression levels of Bcl-2-associated X protein, beclin-1, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and silent information regulation 1 (SIRT1) were significantly upregulated in myocytes following H/R injury. These effects on the expression of these proteins were reversed by curcumin treatment. These findings suggested that the protective effect of curcumin against H/R injury in the H9c2 myocytes was through the inhibition of apoptosis and autophagy by inducing the expression of Bcl-2 and inhibiting the expression levels of Bax, beclin-1, BNIP3 and SIRT1. Therefore, curcumin may offer a promising therapeutic approach for the treatment of cardiomyocyte injury resulting from I/R.

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

“…Autophagy is anti‐apoptotic and contributes to cellular recovery during brief myocardial ischaemia, but the subsequent reperfusion could cause excessive autophagy, which is considered cytotoxic and termed as class II programmed or autophagic cell death 6, 7, 8, 26. Our previous studies showed that inhibiting excessive autophagy could significantly decrease the infarct size and improve cardiac function after I/R‐induced myocardial injury 27, 28. A similar result was observed in vitro in this study.…”

Therapeutic targeting of autophagy in myocardial infarction and heart failure

“…Other molecules such as cloxyquin (a mitochondrial uncoupler and autophagy activator) and the AMPK activator PT1 also display cardioprotective effects during IR by inducing autophagy flux in both in vivo and ex vivo experiments [48,49]. On the other hand, it has not been determined yet whether the cardioprotective effect of curcumin is due to an increase or decrease in cardiomyocyte autophagy, but the currently available evidence suggests that the effects observed might be related to this process [50,51]. In line with a protective role of autophagy, tibetan patients showed an increased cardiac basal autophagy (LC3II, LAMP2, and Bnip3) as a consequence of living at high altitude and thus being exposed to chronic hypoxia [52].…”

Inhibition of LncRNA-HRIM Increases Cell Viability by Regulating Autophagy Levels During Hypoxia/Reoxygenation in Myocytes

“…However, the excessive activation of autophagy degrades some important cell structures, which eventually leads to cell death [29]. Our previous experiments demonstrated that autophagy adversely affects myocardial cells during the H/R period [3, 4] and that inhibition of excessive autophagy increases the viability of myocytes. These results indicated that autophagy regulation is an effective strategy for treating H/R injury.…”

“…During the reperfusion period, inhibition of autophagy with berberine [3] or curcumin [4] significantly mitigates I/R injury, which reduces the scope of MI and improves cardiac function. These findings suggest that excessive autophagy plays an adverse role during I/R period injury.…”