Panax quinquefolium saponin attenuates cardiomyocyte apoptosis and opening of the mitochondrial permeability transition pore in a rat model of ischemia/reperfusion.

Abstract

AIMS:

Opening of the mitochondrial permeability transition pore (mPTP) is a critical event during ischemia/reperfusion (I/R) injury. Recently, we showed that Panax quinquefolium saponin (PQS) alleviates apoptosis of cardiomyocytes by suppressing excessive endoplasmic reticulum stress (ERS) during I/R injury. Here, we hypothesized that this anti-apoptotic effect might be mediated through inhibition of mPTP and the mitochondrial apoptotic pathway.

METHODS:

Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham, I/R, I/R+PQS (200 mg/kg/d), Cyclosporine A (CsA, 10 mg/kg), I/R+CsA (10 mg/kg), and I/R+PQS+CsA. I/R was modeled in rats by ligating the left anterior descending artery (LAD) for 30 min followed by 120 min of reperfusion. To evaluate the cardioprotective function of PQS, we measured hemodynamics, serum content of creatine kinase-MB (CK-MB), myocardial infarct size, and myocardial apoptotic index (AI). We investigated the underlying mechanism by examining changes in the mitochondrial ultrastructure and membrane potential (ΔΨm), dynamics of mPTP opening, expression of cleaved caspase-3, cleaved caspase-9 in the myocardium, Bcl-2 and Bax in the mitochondria versus cytosol, and translocation of cytochrome c.

RESULTS:

Administration of PQS to I/R rats significantly reduced serum CK-MB level, infarct size and AI. In addition, PQS protected the mitochondrial structure, markedly inhibited mPTP opening and ΔΨm depolarization, led to upregulation of Bcl-2 and downregulation of Bax in the mitochondria compared to the cytosol, and suppressed the expression of cleaved caspase-9 and cleaved caspase-3, as well as I/R induced translocation of cytochrome c to the cytoplasm.

CONCLUSION:

Our results show that PQS can alleviate apoptosis of cardiomyocytes during I/R injury, possibly due to repressed mitochondrial apoptotic pathway associated with the opening of mPTP induced by myocardial I/R injury.

• Authors: Dong Li, Mi Liu, Tian-Qi Tao, Dan-Dan Song, Xiu-Hua Liu, Da-Zhuo Shi
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 34 Issue 4 Pg. 1413-26 ( 2014) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25301366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Panax quinquefolium saponin
• Proto-Oncogene Proteins c-bcl-2
• Saponins
• bcl-2-Associated X Protein
• Cyclosporine
• Cytochromes c
• Caspase 3
• Caspase 9

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cyclosporine (pharmacology)
• Cytochromes c (metabolism)
• Cytosol (drug effects, metabolism)
• Endoplasmic Reticulum Stress (drug effects)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Permeability Transition Pore
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism)
• Saponins (pharmacology)
• bcl-2-Associated X Protein (metabolism)