NGFI-B targets mitochondria and induces cardiomyocyte apoptosis in restraint-stressed rats by mediating energy metabolism disorder.
NGFI-B/Nur77/TR3, originally identified as an immediate-early gene rapidly induced by serum and growth factors, is a member of the steroid hormone nuclear receptor superfamily with no identified endogenous ligand. NGFI-B induces apoptosis in a number of cell lineages exposed to proapoptotic stimuli by directly targeting the mitochondria, inducing cytochrome c release. The present study was designed to determine the role of NGFI-B in cardiomyocytes of restraint-stressed rats. The NGFI-B content was increased in mitochondria and reduced in plasma as apoptosis increased. Analysis showed that NGFI-B induces cardiomyocyte apoptosis in restraint-stressed rats by mediating mitochondrial energy metabolism disorder. Several novel mitochondrial proteins, which correlate with NGFI-B, were reported in cardiomyocyte apoptosis of restraint-stressed rats. Five proteins associated with NGFI-B participate directly in mitochondrial energy metabolism. Studies of mitochondrial respiratory efficiency and ATP synthase activity strongly support the findings. These results provide significant information for comprehensively understanding the cellular mechanism of cardiovascular diseases.
Wang
XinXing
X
Department of Stress Medicine, Institute of Health & Environmental Medicine, No.1 DaLi Road, Tianjin 300050, People's Republic of China.
Liu
XiaoHua
X
Kong
RuiRui
R
Zhan
Rui
R
Wang
XiaoMing
X
Leng
Xue
X
Gong
JingBo
J
Duan
Meng
M
Wang
LiQun
L
Wu
Lei
L
Qian
LingJia
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D019069:Cell Respiration; D004734:Energy Metabolism / Q000502:physiology*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D051381:Rats; D012149:Restraint, Physical
D024101:Mitochondrial Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D025261:Mitochondrial Proton-Translocating ATPases