Superoxide stimulation enhances CXCR4 expression in heart muscle-derived stem cells via ASK1 activation

Background: Stem cell therapy for cardiac regeneration is hindered by poor homing to infarcted legion because of poor expression of homing factor, CXCR4, on the stem cell surface. A strategy for enhancing CXCR4 is promising to accelerate stem cell homing to infarcted lesion. Methods and Results: Heart muscle-derived Sca-1(+) cells (HDSCs) were isolated from normal mouse heart using surface antigen Sca-1. The expression of CXCR4 was determined by the fluorescence-activated cell sorting by labeling the cells with CXCR4 antibody with fluorescence. The expression of CXCR4 was enhanced by stimulation of hydrogen peroxide (0.1, 0.33, 1μM) for 24h. The Western blotting showed no significant increase in the protein level of CXCR4. The enhancement of CXCR4 can be attributed to translocation of CXCR4 from the cytosolic fraction to cell surface. H2O2 stimulation enhanced ASK1 p966 phosphorylation. Conclusions: The expression of CXCR4 on HDSCs was augmented by H2O2 through the translocation from cytosolic to membrane surface through ASK1 phosphorylation.