N-n-butyl haloperidol iodide protects cardiac microvascular endothelial cells from hypoxia/reoxygenation injury by down-regulating Egr-1 expression.

Abstract

AIMS:

Our previous studies have shown that N-n-butyl haloperidol iodide (F2) can antagonize myocardial ischemia/reperfusion (I/R) injury by down-regulating the early growth response (Egr)-1 expression, but the molecular mechanisms are not well understood. Because there is evidence implicating myocardial I/R injury is closely associated with endothelial dysfunction. The present study is to test the hypothesis that the protective effects of F2 on myocardial I/R injury is related closely with down-regulating Egr-1 expression on cardiac microvascular endothelial cells (CMECs).

METHODS:

A model of cultured CMECs exposed to hypoxia/reoxygenation (H/R) was developed. With antisense Egr-1 oligodeoxyribonucleotide (ODN), the relationship between Egr-1 expression and endothelial H/R injury was investigated. Egr-1 mRNA and protein expression were examined by real-time fluorescent quantitative PCR, immunocytochemical staining and Western-blot analysis. Lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), intercellular adhesion molecule-1 (ICAM-1), adherence of neutrophil and platelets, and cell viability were measured after H/R to evaluate the degree of endothelial injury.

RESULTS:

Pretreatment with antisense Egr-1 ODN significantly reduced Egr-1 protein expression and attenuated injury of CMECs. Consistent with down-regulation of Egr-1 expression by F2, inflammation and other damage were significantly reduced as evidenced by a decrease of ICAM-1 expression, reduction of neutrophil and platelets adherence, increase in SOD, and decreases in MDA and LDH levels, resulting in the rise of cell viability.

CONCLUSIONS:

We demonstrate a protective effect of F2 in CMECs against H/R injury by down-regulating Egr-1 expression, which might be play a vital role in the pathogenesis of myocardial I/R injury.

• Authors: Yanqiong Zhou, Yanmei Zhang, Fenfei Gao, Fuxiao Guo, Jinzhi Wang, Wenfeng Cai, Yicun Chen, Jinhong Zheng, Ganggang Shi
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 26 Issue 6 Pg. 839-48 ( 2010) ISSN: 1421-9778 [Electronic] Germany
• PMID: 21220915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 S. Karger AG, Basel.

Chemical References

• Early Growth Response Protein 1
• N-n-butyl haloperidol iodide
• Oligodeoxyribonucleotides, Antisense
• Intercellular Adhesion Molecule-1
• Malondialdehyde
• L-Lactate Dehydrogenase
• Superoxide Dismutase
• Haloperidol

Topics

• Animals
• Blood Platelets (physiology)
• Cell Adhesion
• Cell Hypoxia
• Cell Survival
• Cells, Cultured
• Down-Regulation
• Early Growth Response Protein 1 (genetics, metabolism, physiology)
• Endothelial Cells (cytology, metabolism)
• Endothelium, Vascular (cytology)
• Female
• Haloperidol (analogs & derivatives, pharmacology)
• Intercellular Adhesion Molecule-1 (metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Malondialdehyde (metabolism)
• Myocardial Reperfusion Injury (genetics, metabolism)
• Myocardium (cytology)
• Neutrophils (immunology, physiology)
• Oligodeoxyribonucleotides, Antisense (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Superoxide Dismutase (metabolism)