期刊
ONCOGENE
卷 24, 期 11, 页码 1895-1903出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1208262
关键词
mitochondrial dysfunction; TGF beta 1; senescence; reactive oxygen species; complex IV defect
Transforming growth factor beta 1 (TGF beta 1) is a well-characterized cytokine that suppresses epithelial cell growth. We report here that TGF beta 1 arrested lung epithelial Mv1Lu cells at G1 phase of the cell cycle with acquisition of senescent phenotypes in the presence of 10% serum, whereas it gradually induced apoptosis with lower concentrations of serum. The senescent arrest was accompanied by prolonged generation of reactive oxygen species (ROS) and persistent disruption of mitochondrial membrane potential (Delta psi m). We demonstrated that the sustained ROS overproduction was derived from mitochondrial respiratory defect via decreased complex IV activity and was involved in the arrest. Moreover, we verified that hepatocyte growth factor released Mv1Lu cells from the arrest by protecting mitochondrial respiration, thereby preventing both the Delta psi m disruption and the ROS generation. Our present results suggest the TGF beta 1-induced senescent arrest as another plausible mechanism to suppress cellular growth in vivo and provide a new biochemical association between the mitochondrial functional defects and the cytokine-induced senescent arrest, emphasizing the importance of maintenance of mitochondrial function in cellular protection from the arrest.
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