Abstract 19185: Upregulation of DJ-1 Protein after Prolonged Ischemia in a Murine Model for Myocardial Ischemia and Reperfusion
Introduction: Upregulation of cardiac DJ-1 protein might be a cardio-protective mechanism under conditions of ischemia or ischemia and reperfusion by regulating mitogen activated protein (MAP) kinases or inducing enzymes for detoxification and glutathione metabolism. We recently observed that significantly elevated DJ-1 protein expression was associated with decreased expression of phosphatase and tensin homolog (PTEN) and increased phosphorylation of the cell protective kinase AKT (protein kinase B) in human heart tissue samples from patients with chronic ischemic cardiomyopathy.
Hypothesis: The expression of DJ-1 protein and its interaction with PTEN and AKT during ischemia or ischemia and reperfusion in a murine heart model might play a cardio-protective role.
Methods: The level of DJ-1 was analyzed from the area at risk after 30 or 60-minute ischemia or 30-minute ischemia with 30 or 60 minutes of reperfusion using C57BL/6J mice (n=3). The changes in DJ-1 expression were correlated with the expression of PTEN and AKT and phosphorylation of ERK1/2 (extracellular signal regulated kinase) and P38. The protein levels and their phosphorylation were evaluated by Western blot analysis.
Results: Expression of DJ-1 increased significantly after 60 minutes of ischemia while PTEN decreased after 30 minutes of ischemia followed by 30 or 60 minutes of reperfusion both were associated with increased phosphorylation of AKT. The phosphorylation of ERK1/2 was increased at all time points of ischemia or ischemia and reperfusion while phosphorylation of P38 was increased only during ischemia and reperfusion.
Conclusions: The increased expression of DJ-1 protein is a potential marker for prolonged ischemia. Although, PTEN expression were not decreased with increased DJ-1 levels, a direct inhibiting effect of DJ-1 on PTEN might increase the phosphorylation of the cell protective AKT during 60-minute ischemia. A DJ-1 independent decrease of PTEN expression might contribute to the increased AKT phosphorylation during ischemia reperfusion. Phosphorylation of ERK1/2 was a sensitive marker of early or late ischemia and ischemia and reperfusion. The role of the DJ-1-AKT interaction in preventing P38 phosphorylation during ischemia needs further investigation.
Author Disclosures: T. Seres: None. J. Klawitter: None. U. Christians: None. T. Eckle: None.
- © 2014 by American Heart Association, Inc.