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Ischemic preconditioning, insulin, and morphine all cause hexokinase redistribution
Coert J Zuurbier1, Otto Eerbeek, Alfred J Meijer
1Dept. of Anesthesiology, Academic Medical Center, Univ. of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.j.zuurbier@amc.uva.nl
Summary
Cardioprotective interventions like insulin and morphine promote hexokinase (HK) movement to mitochondria. This translocation preserves heart cell integrity and reduces cell death, offering a novel therapeutic insight.
Area of Science:
- Biochemistry
- Cardiology
- Cell Biology
Background:
- Hexokinase (HK) association with mitochondria is crucial for preserving mitochondrial integrity, particularly in cancer cells under hypoxia.
- Maintaining mitochondrial integrity is a hallmark of effective cardioprotective strategies.
Purpose of the Study:
- To investigate whether cardioprotective interventions induce the redistribution of hexokinase (HK) from the cytosol to mitochondria in cardiac tissue.
- To identify a common molecular mechanism underlying various cardioprotective interventions.
Main Methods:
- Isolated Langendorff-perfused rat hearts were subjected to normoxic perfusion, ischemic preconditioning (IPC), insulin (Ins), or morphine (Mor).
- Hearts were fractionated into cytosolic and mitochondrial components.
- Enzyme activities of hexokinase (HK), lactate dehydrogenase (LDH), and citrate synthase (CS) were measured in each fraction.
Main Results:
- Cardioprotective interventions significantly decreased cytosolic HK levels relative to total cellular activity.
- Concurrently, HK levels relative to citrate synthase activity increased significantly in the mitochondrial fraction following IPC, insulin, and morphine treatments.
- No significant changes in cytosolic lactate dehydrogenase or citrate synthase were observed, indicating specific HK translocation.
Conclusions:
- Well-established cardioprotective interventions share a common mechanism involving the translocation of cytosolic hexokinase (HK) to mitochondria.
- This HK redistribution to mitochondria may inhibit the mitochondrial permeability transition pore, thereby reducing cardiac cell death and apoptosis.
- The findings suggest a novel therapeutic target for preventing heart damage.