Intermittent hypoxia-generated ROS contributes to intracellular zinc regulation that limits ischemia/reperfusion injury in adult rat cardiomyocyte

Chih Feng Lien, Wen Sen Lee, I. Chieh Wang, Tsung I. Chen, Tzu Lin Chen, Kun Ta Yang

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4 Citations (Scopus)


Intermittent hypoxia (IH) has been shown to exert cardioprotective effects against ischemia/reperfusion (I/R) injury through the preservation of ion homeostasis. I/R dramatically elevated cytosolic Zn2+ and caused cardiomyocyte death. However, the role of IH exposure in the relationship between Zn2+ regulation and cardioprotection is still unclear. The aim of the present study was to study whether IH exposure could help in intracellular Zn2+ regulation, hence contributing to cardioprotection against I/R injury. Adult rat cardiomyocytes were exposed to IH (5% O2, 5% CO2 and balanced N2) for 30 min followed by 30 min of normoxia (21% O2, 5% CO2 and balanced N2). Changes in intracellular Zn2+ concentration were determined using a Zn2+-specific fluorescent dye, FluoZin-3 or RhodZin-3. Fluorescence was monitored under an inverted fluorescent or confocal microscope. The results demonstrated that I/R or 2,2′-dithiodipyridine (DTDP), a reactive disulphide compound, induced Zn2+ release from metallothioneins (MTs), subsequently causing cytosolic Zn2+ overload, which in turn increased intracellular Zn2+ entry into the mitochondria via a Ca2+ uniporter, hence inducing mitochondrial membrane potential loss, and eventually led to cell death. However, the cytosolic Zn2+ overload and cell death caused by I/R or DTDP was significantly reduced by treatment of cardiomyocytes with IH. The findings from this study suggest that IH might exert its cardioprotective effect through reducing the I/R-induced cytosolic Zn2+ overload and cell death in cardiomyocytes.

Original languageEnglish
Pages (from-to)122-132
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Publication statusPublished - May 1 2018



  • Cardioprotection
  • Intermittent hypoxia
  • Intracellular zinc
  • Ischemia/reperfusion
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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