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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
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Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress

Chen Wang1, Jian Chen2, Mengxue Wang1

  • 1Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

Biochemical and Biophysical Research Communications
|June 18, 2021
PubMed

Insights

Blocking the TRPM4 channel protects heart cells from oxidative stress. This mechanism preserves mitochondrial function and ATP levels, crucial for preventing cell death during ischemia-reperfusion injury.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Ischemic heart disease is a leading global cause of mortality.
  • Ischemia-reperfusion (I/R) injury involves mitochondrial dysfunction, reactive oxygen species (ROS) generation, and calcium (Ca2+) overload.
  • TRPM4 channel inhibition shows cardioprotective effects in I/R injury, but the mechanism is not fully understood.

Purpose of the Study:

  • To investigate the cardioprotective mechanism of TRPM4 inhibition against I/R injury.
  • To elucidate the role of TRPM4 in oxidative stress-induced myocardial damage.
  • To examine the impact of TRPM4 knockout on cellular and mitochondrial function during oxidative stress.

Main Methods:

  • Utilized CRISPR/Cas9 to generate TRPM4 knockout (TRPM4KO) in H9c2 rat cardiomyocyte cell line.
  • Induced oxidative stress using hydrogen peroxide (H2O2) as an I/R injury model.
  • Assessed intracellular Ca2+ levels, ROS production, mitochondrial membrane potential (ΔΨm), and intracellular ATP levels.

Main Results:

  • H2O2 treatment increased intracellular Ca2+ and ROS in wild-type (WT) cells, but not in TRPM4KO cells.
  • Mitochondrial function indicators (ΔΨm and ATP levels) decreased in WT cells but remained stable in TRPM4KO cells following H2O2 exposure.
  • TRPM4 knockout prevented H2O2-induced cellular damage and mitochondrial dysfunction.

Conclusions:

  • TRPM4 channel blockade may protect the myocardium from oxidative stress.
  • This protection is potentially mediated by maintaining mitochondrial membrane potential and intracellular ATP levels.
  • Preventing aberrant increases in intracellular Ca2+ and ROS appears to be a key aspect of TRPM4-mediated cardioprotection.
Keywords:
CRISPR/Cas9CalciumMitochondrial functionMyocardial ischemia-reperfusion injuryReactive oxygen speciesTRPM4

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