Phosphorylated nerve growth factor-induced clone B (NGFI-B) translocates from the nucleus to mitochondria of stressed rat cardiomyocytes and induces apoptosis

Stress induces cardiac dysfunction and cardiomyocyte injury, and while current data indicate that mitochondria play a key role in this process, the mechanisms remain unknown. In this study, we found that in rats, restraint stress induced nerve growth factor-induced clone B (NGFI-B) translocation from the nucleus to mitochondria in cardiomyocytes. This translocation promoted cytochrome c release from mitochondria to the cytoplasm, which ultimately resulted in cardiomyocyte apoptosis. We also found that stress induced oversecretion of glucocorticoids and activated the protein kinase A (PKA) pathway in cardiomyocytes. Enhanced PKA activity increased NGFI-B serine phosphorylation, which caused NGFI-B to translocate from the nucleus to mitochondria. Moreover, a PKA peptide inhibitor blocked NGFI-B serine phosphorylation and translocation. Our data demonstrate that stress affects cardiomyocytes by inducing NGFI-B mitochondrial translocation via serine phosphorylation, which in turn initiates mitochondrial-mediated apoptosis.