Baicalein inhibits mitochondrial apoptosis induced by oxidative stress in cardiomyocytes by stabilizing MARCH5 expression

J Cell Mol Med. 2020 Jan;24(2):2040-2051. doi: 10.1111/jcmm.14903. Epub 2019 Dec 27.

Abstract

Abnormal mitochondrial fission and mitophagy participate in the pathogenesis of many cardiovascular diseases. Baicalein is a key active component in the roots of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. It has been reported that baicalein can resist cardiotoxicity induced by several stress, but the mechanisms of baicalein operate in the protection of cardiomyocytes need to be researched further. Here we report that baicalein can promote cell survival under oxidative stress by up-regulating the expression level of MARCH5 in cardiomyocytes. Pre-treatment cells or mice with baicalein can stabilize the expression of MARCH5, which plays a crucial role in the regulation of mitochondrial network and mitophagy. Overexpressed MARCH5 is able to against H2 O2 and ischaemia/reperfusion (I/R) stress by suppressing mitochondrial fission and enhancing mitophagy, and then attenuate cells apoptosis. Altogether, our present study investigated that baicalein exerts a protective effect through regulating KLF4-MARCH5-Drp1 pathway, our research also provided a novel theoretical basis for the clinical application of baicalein.

Keywords: MARCH5; apoptosis; baicalein; cardioprotection; mitophagy; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cardiotonic Agents / pharmacology
  • Cell Line
  • Flavanones / pharmacology*
  • Flavanones / therapeutic use
  • Hydrogen Peroxide / toxicity*
  • Kruppel-Like Factor 4
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics / drug effects
  • Mitochondrial Proteins / metabolism*
  • Mitophagy / drug effects
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology*
  • Oxidative Stress / drug effects*
  • Protein Stability / drug effects
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Cardiotonic Agents
  • Flavanones
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Mitochondrial Proteins
  • baicalein
  • Hydrogen Peroxide
  • Marchf5 protein, mouse
  • Ubiquitin-Protein Ligases