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Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
Minoxidil attenuates ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes
Tomoka Takatani1, Kyoko Takahashi, Chengshi Jin
1Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Abstract:
The effects of minoxidil (a mitochondrial K+(ATP) channel opener) on ischemia-induced necrosis and apoptosis were examined using a cardiomyocyte model of simulated ischemia, since mitochondrial K+(ATP) channel openers have been suggested to be involved in the mechanisms of cardioprotective action against ischemia/reperfusion injury. In the absence of minoxidil, simulated ischemia led to cellular release of creatine phosphokinase (CPK), morphologic degeneration, and beating cessation within 24 to 72 hours. Based on the Hoechst 33258 staining pattern, a significant number of cells placed in sealed flasks underwent apoptosis. Myocytes treated with 5 microM of minoxidil failed to alter the degree of ischemia-induced CPK loss for 48 to 72 hours. However, minoxidil treatment prevented the loss of beating function in many of the ischemic cells, and attenuated the decline in intracellular ATP content after a 48-hour ischemic incubation. The number of nuclear fragmentation was significantly reduced in minoxidil-treated cells after a 72-hour ischemic insult compared with untreated ischemic cells. This effect was blocked by the mitochondrial K+(ATP) channel antagonist 5-HD. The data suggest that minoxidil renders the cell resistant to ischemia-induced necrosis and apoptosis. The beneficial effects of minoxidil appear to be related to the opening of mitochondrial K+(ATP) channels.
Insights
Minoxidil protects heart cells from death during simulated ischemia by opening mitochondrial K+(ATP) channels. This drug reduces necrosis and apoptosis, preserving cell function and ATP levels.
Area of Science:
- Cardiovascular Science
- Cell Biology
- Pharmacology
Background:
- Mitochondrial K+(ATP) channels are implicated in cardioprotection against ischemia/reperfusion injury.
- Simulated ischemia in cardiomyocytes induces necrosis, apoptosis, and loss of function.
Purpose of the Study:
- To investigate the effects of minoxidil, a mitochondrial K+(ATP) channel opener, on ischemia-induced necrosis and apoptosis in cardiomyocytes.
- To determine if minoxidil confers cardioprotection by modulating mitochondrial K+(ATP) channels.
Main Methods:
- A cardiomyocyte model of simulated ischemia was used.
- Cells were treated with minoxidil (5 microM) or vehicle control.
- Creatine phosphokinase (CPK) release, cell morphology, beating function, intracellular ATP content, and nuclear fragmentation (apoptosis) were assessed.
- The effect of the mitochondrial K+(ATP) channel antagonist 5-HD was evaluated.
Main Results:
- Minoxidil did not prevent CPK release but preserved beating function and attenuated ATP decline in ischemic cardiomyocytes.
- Minoxidil significantly reduced nuclear fragmentation, indicating decreased apoptosis.
- The protective effects of minoxidil were blocked by 5-HD, confirming the role of mitochondrial K+(ATP) channels.
Conclusions:
- Minoxidil confers resistance to ischemia-induced necrosis and apoptosis in cardiomyocytes.
- The cardioprotective effects of minoxidil are mediated through the opening of mitochondrial K+(ATP) channels.
