Puerarin Attenuates Anoxia/Reoxygenation Injury Through Enhancing Bcl-2 Associated Athanogene 3 Expression, a Modulator of Apoptosis and Autophagy.

Abstract

BACKGROUND:

Puerarin has protective effects on ischemia-reperfusion injury, but the underlying mechanisms are not fully revealed. This study explored the effect of puerarin on the expression of Bcl-2 associated athanogene 3 (BAG3) in an in vitro model of anoxia/reoxygenation injury (A/RI) in neonate rat primary cardiomyocytes and the functions of BAG3 in A/RI.

MATERIAL/METHODS:

BAG3 expression in cardiomyocytes with or without puerarin pre-treatment was quantified using qRT-PCR and Western blot analysis. The effects of BAG3 on A/RI were studied by measuring the activity of lactate dehydrogenase (LDH) and creatine phosphate kinase (CPK), the concentration of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The effects of BAG3 on autophagy and apoptosis of the cardiomyocytes after A/RI were further studied.

RESULTS:

Puerarin significantly promoted BAG3 expression in the rat primary cardiomyocytes after A/RI. Enforced BAG3 expression presented similar effects as puerarin pre-treatment in attenuating A/RI in terms of CPK, LDH, MDA, SOD, GSH-Px, ROS generation, and cell viability. BAG3 overexpression significantly stimulated autophagy in cardiomyocytes after A/RI, which presented protective effects on A/RI in terms of cell viability and apoptosis. Autophagy inhibition partly abrogated the protective effects of BAG3.

CONCLUSIONS:

Puerarin can directly increase BAG3 transcription and translation in cardiomyocytes after A/RI. The elevated BAG3 expression presents protective effects on A/RI at least through enhancing autophagy and reducing apoptosis, which is a novel protective mechanism of puerarin in ARI.

• Authors: Yayu Ma, Ya Gai, Jingpeng Yan, Jian Li, Yangyang Zhang
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 22 Pg. 977-83 (Mar 24 2016) ISSN: 1643-3750 [Electronic] United States
• PMID: 27011313 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAG3 protein, rat
• Isoflavones
• Reactive Oxygen Species
• Malondialdehyde
• L-Lactate Dehydrogenase
• Glutathione Peroxidase
• Superoxide Dismutase
• Creatine Kinase
• Oxygen
• puerarin

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Autophagy (drug effects)
• Cell Hypoxia (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Creatine Kinase (metabolism)
• Glutathione Peroxidase (metabolism)
• Isoflavones (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Malondialdehyde (metabolism)
• Myocytes, Cardiac (drug effects, enzymology, pathology)
• Oxygen (pharmacology)
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)