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NMDA receptor-driven calcium influx promotes ischemic human cardiomyocyte apoptosis through a p38 MAPK-mediated

Zi-You Liu1, Qin-Wen Zhong1, Cheng-Nan Tian1

  • 1Heart Center, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.

Journal of Cellular Biochemistry
|January 8, 2019
PubMed

Insights

N-methyl-D-aspartate receptor (NMDAR) activity increases calcium influx, cell death, and apoptosis in oxygen-glucose deprivation (OGD) cardiomyocytes. Blocking NMDAR or p38 mitogen-activated protein kinase (MAPK) activity protects these cells during myocardial ischemia.

Area of Science:

  • Cardiology
  • Neuroscience
  • Cell Biology

Background:

  • N-methyl-D-aspartate receptor (NMDAR) is crucial in cerebral ischemia.
  • NMDAR is present in cardiomyocytes, but its role in myocardial ischemia is understudied.

Purpose of the Study:

  • To investigate NMDAR activity's effects on calcium influx, viability, and apoptosis in an in vitro cardiomyocyte ischemia model.
  • To explore the involvement of mitogen-activated protein kinases (MAPKs) in NMDAR-mediated effects during myocardial ischemia.

Main Methods:

  • Primary human neonatal cardiomyocytes were subjected to oxygen-glucose deprivation (OGD) to simulate ischemia.
  • NMDAR activity was modulated using NMDA, MK-801, and calcium channel blockers.
  • p38 MAPK activity was inhibited using small molecules and genetic methods.

Main Results:

  • Enhanced NMDAR activity significantly increased calcium influx, decreased cell viability, and promoted apoptosis in OGD cardiomyocytes.
  • NMDAR-induced apoptosis was linked to increased p38 MAPK phosphorylation.
  • Inhibition of NMDAR or p38 MAPK activity significantly improved cell viability and reduced apoptosis.

Conclusions:

  • NMDAR-driven calcium influx exacerbates apoptosis in ischemic human cardiomyocytes.
  • Enhanced p38 MAPK activity mediates NMDAR-induced apoptosis.
  • Targeting NMDAR or p38 MAPK pathways may offer therapeutic strategies for myocardial ischemia.
Keywords:
N-methyl-D-aspartate receptor (NMDAR)NMDAcardiomyocyteischemiamyocardialoxygen-glucose deprivation (OGD)

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