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

Mol Med Rep. 2015 Jun;11(6):4678-84. doi: 10.3892/mmr.2015.3322. Epub 2015 Feb 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Beclin-1
  • Cell Hypoxia
  • Cell Line
  • Curcumin / pharmacology*
  • Down-Regulation / drug effects
  • Humans
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Oxygen / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sirtuin 1 / metabolism
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • BNIP3 protein, human
  • Beclin-1
  • MAP1LC3B protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • SIRT1 protein, human
  • Sirtuin 1
  • Curcumin
  • Oxygen