Helix B Surface Peptide Protects against Acute Myocardial Ischemia-Reperfusion Injury via the RISK and SAFE Pathways in a Mouse Model.

Abstract

OBJECTIVE:

This study explores the effects of helix B surface peptide (HBSP) on myocardial infarct size (IS), cardiac function, cardiomyocyte apoptosis and oxidative stress damage in mouse hearts subjected to myocardial ischemia-reperfusion injury (MIRI) and also the mechanisms underlying the effects.

METHOD:

Male adult mice were subjected to 45 min of ischemia followed by 2 h of reperfusion; 5 min before the reperfusion, they were treated with HBSP or vehicle. MIRI-induced IS, cardiomyocyte apoptosis and cardiac functional impairment were determined and compared. Western blot analysis was then conducted to elucidate the mechanism of HBSP after treatment.

RESULTS:

HBSP administration before reperfusion significantly reduced the myocardial IS, decreased cardiomyocyte apoptosis, reduced the activities of superoxide dismutase and malondialdehyde and partially preserved heart function. As demonstrated by the Western blot analysis, HBSP after treatment upregulated Akt/GSK-3β/ERK and STAT-3 phosphorylation; these inhibitors, in turn, weakened the beneficial effects of HBSP.

CONCLUSION:

HBSP plays a protective role in MIRI in mice by inhibiting cardiomyocyte apoptosis, reducing the MIRI-induced IS, oxidative stress and improving the heart function after MIRI. The mechanism underlying these effects of HBSP is related to the activation of the RISK (reperfusion injury salvage kinase, Akt/GSK-3β/ERK) and SAFE (STAT-3) pathways.

• Authors: Peng Liu, Wei You, Lin Lin, Yongluan Lin, Xiuying Tang, Yingfeng Liu, Fei Miao
• Journal: Cardiology (Cardiology) Vol. 134 Issue 2 Pg. 109-17 ( 2016) ISSN: 1421-9751 [Electronic] Switzerland
• PMID: 26938973 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 S. Karger AG, Basel.

Chemical References

• Peptide Fragments
• glutaminyl-glutamyl-glutaminyl-leucyl-glutamyl-arginyl-alanyl-leucyl-asparagyl-seryl-serine
• Erythropoietin

Topics

• Animals
• Apoptosis (drug effects)
• Disease Models, Animal
• Erythropoietin (administration & dosage)
• Male
• Mice
• Myocardial Reperfusion Injury (drug therapy)
• Myocytes, Cardiac (drug effects)
• Peptide Fragments (administration & dosage)
• Phosphorylation
• Signal Transduction (drug effects)
• Ventricular Function (drug effects)