Key result
N-n-butyl haloperidol iodide protects cardiac microvascular endothelial cells against hypoxia-reoxygenation injury by downregulating Egr-1.
Why the study?
The molecular mechanisms by which N-n-butyl haloperidol iodide (F2) protects against myocardial ischemia/reperfusion injury via down-regulating Egr-1 expression are not well understood, particularly in cardiac microvascular endothelial cells.
Does N-n-butyl haloperidol iodide protect cultured cardiac microvascular endothelial cells from hypoxia/reoxygenation injury?
Does N-n-butyl haloperidol iodide protect cultured cardiac microvascular endothelial cells from hypoxia/reoxygenation injury?
N-n-butyl haloperidol iodide protects cardiac microvascular endothelial cells against hypoxia/reoxygenation injury by down-regulating Egr-1 expression.
Should not alter clinical management of ischemia-reperfusion injury; hypothesis-generating for Egr-1 targeting in microvascular endothelium.
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.
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Zhou et al. (2010) studied Myocardial ischemia/reperfusion injury. N-n-butyl haloperidol iodide (F2) was evaluated on Egr-1 expression, inflammation, and cell viability. N-n-butyl haloperidol iodide protected cardiac microvascular endothelial cells against hypoxia/reoxygenation injury by down-regulating Egr-1 expression and reducing inflammation and cell damage.
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