title: Phosphorylated nerve growth factor-induced clone B (NGFI-B) translocates from the nucleus to mitochondria of stressed rat cardiomyocytes and induces apoptosis.
abstract: 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.
authors: Institute of Health & Environmental Medicine, Tianjin, China.
authors: Wang
authors: W
authors: Xinxing
authors: Feng
authors: F
authors: Hong
authors: Zhan
authors: Z
authors: Rui
authors: Zhao
authors: Z
authors: Yun
authors: Gong
authors: G
authors: Jingbo
authors: Qian
authors: Q
authors: Lingjia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological
chemical_list: D024101:Mitochondrial Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D045304:Cytochromes c