Title

Role Of Omi/Htra2 In Apoptotic Cell Death After Myocardial Ischemia And Reperfusion

Keywords

Apoptosis; Myocardial infarction; Reperfusion

Abstract

Background - Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent as well as caspase-independent cell death. However, the role of Omi/HtrA2 in the apoptotic cell death that occurs in vivo under pathological conditions remains unknown. The present study was designed to investigate whether Omi/HtrA2 plays an important role in postischemic myocardial apoptosis. Methods and Results - Male adult mice were subjected to 30 minutes of myocardial ischemia followed by reperfusion and treated with vehicle or ucf-101, a novel and specific Omi/HtrA2 inhibitor, 10 minutes before reperfusion. Myocardial ischemia/reperfusion significantly increased cytosolic Omi/HtrA2 content and markedly increased apoptosis. Treatment with ucf-101 exerted significant cardioprotective effects, as evidenced by less terminal dUTP nick end-labeling staining, a lower incidence of DNA ladder fragmentation, and smaller infarct size. Furthermore, treatment with ucf-101 before reperfusion attenuated X-linked inhibitor of apoptosis protein degradation and inhibited caspase-9 and caspase-3 activities. Conclusion - Taken together, these results demonstrate for the first time that ischemia/reperfusion results in Omi/HtrA2 translocation from the mitochondria to the cytosol, where it promotes cardiomyocyte apoptosis via a protease activity-dependent, caspase-mediated pathway.

Publication Date

1-4-2005

Publication Title

Circulation

Volume

111

Issue

1

Number of Pages

90-96

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1161/01.CIR.0000151613.90994.17

Socpus ID

19944429185 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/19944429185

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