1. Academic Validation
  2. Role of Omi/HtrA2 in apoptotic cell death after myocardial ischemia and reperfusion

Role of Omi/HtrA2 in apoptotic cell death after myocardial ischemia and reperfusion

  • Circulation. 2005 Jan 4;111(1):90-6. doi: 10.1161/01.CIR.0000151613.90994.17.
Hui-Rong Liu 1 Erhe Gao Aihua Hu Ling Tao Yan Qu Patrick Most Walter J Koch Theodore A Christopher Bernard L Lopez Emad S Alnemri Antonis S Zervos Xin L Ma
Affiliations

Affiliation

  • 1 Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pa, USA.
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.

Conclusions: 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.

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