| First Author | Handayaningsih AE | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 425 |
| Issue | 2 | Pages | 478-84 |
| PubMed ID | 22877754 | Mgi Jnum | J:187153 |
| Mgi Id | MGI:5435614 | Doi | 10.1016/j.bbrc.2012.07.140 |
| Citation | Handayaningsih AE, et al. (2012) IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway. Biochem Biophys Res Commun 425(2):478-84 |
| abstractText | Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated beta-galactosidase (SA-beta-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, gammaH2AX, the increased levels of p53 and p21 proteins, and activated SA-beta-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-beta-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. |
