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Updated: Jul 20, 2026
13:42
Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria
Published on: September 7, 2012
Cardiac mitochondrial cGMP stimulates cytochrome c release
Kazuhiko Seya1, Shigeru Motomura, Ken-Ichi Furukawa
1Department of Pharmacology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Clinical Science (London, England : 1979)
|September 12, 2006
Summary
Cardiac mitochondrial cyclic guanosine monophosphate (cGMP) accelerates cytochrome c release, promoting cardiomyocyte apoptosis independently of mitochondrial permeability transition. This suggests a novel mechanism in heart cell death.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Physiology
- Cell Death Pathways
Background:
- The role of cardiac mitochondrial cyclic guanosine monophosphate (cGMP) in physiological and pathophysiological processes remains largely unexplored.
- Previous studies confirmed the existence of cardiac mitochondrial cGMP, but its specific functions, particularly in cardiomyocyte apoptosis, were unknown.
Purpose of the Study:
- To investigate whether cardiac mitochondrial cGMP regulates the apoptosis of cardiomyocytes.
- To elucidate the mechanism by which cGMP influences cardiomyocyte cell death.
Main Methods:
- Purification of cardiac mitochondria from rat ventricular myocytes.
- Measurement of cGMP levels in response to nitric oxide (NO) donors (SNAP, SNP) and inhibition by ODQ.
- Assessment of cytochrome c release, mitochondrial swelling, and membrane depolarization in isolated mitochondria.
- Induction of apoptosis in primary cultured adult rat cardiomyocytes using SNAP and hypoxia/re-oxygenation, with ODQ as an inhibitor.
Main Results:
- NO donors significantly increased mitochondrial cGMP levels, an effect inhibited by ODQ.
- SNAP and 8-bromo-cGMP, but not cGMP, induced cytochrome c release from energized mitochondria without MPT activation.
- SNAP-induced cytochrome c release and cardiomyocyte apoptosis were inhibited by ODQ.
- ODQ also inhibited apoptosis induced by hypoxia/re-oxygenation in cultured cardiomyocytes.
Conclusions:
- Increased cardiac mitochondrial cGMP production stimulates cytochrome c release from mitochondria.
- This release occurs independently of the mitochondrial permeability transition (MPT).
- cGMP-mediated cytochrome c release is a key mechanism leading to cardiomyocyte apoptosis.
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