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Hyperoxia Induces Macrophage Cell Cycle Arrest by Adhesion-dependent Induction of p21 Cip1 and Activation of the Retinoblastoma Protein
Journal article   Open access   Peer reviewed

Hyperoxia Induces Macrophage Cell Cycle Arrest by Adhesion-dependent Induction of p21 Cip1 and Activation of the Retinoblastoma Protein

Toru Nyunoya, Linda S Powers, Timur O Yarovinsky, Noah S Butler, Martha M Monick and Gary W Hunninghake
The Journal of biological chemistry, Vol.278(38), pp.36099-36106
09/19/2003
DOI: 10.1074/jbc.m304370200
PMID: 12847100
url
https://doi.org/10.1074/jbc.m304370200View
Published (Version of record) Open Access

Abstract

yperoxia induces growth arrest, apoptosis, necrosis, and morphological changes (spreading and adhesion) in various types of cells. The mechanism of hyperoxia-induced cell growth arrest has not been well elucidated, especially in macrophages. One possible mechanism is a role of cell adhesion in hyperoxia-induced cell cycle arrest. To evaluate this finding, macrophages were cultured in normoxia (21% O2) or hyperoxia (95% O2) in adhesion or low adhesion conditions. Incubation of macrophages in hyperoxia induced cell cycle arrest. The hyperoxia-induced cell cycle arrest was prevented by low adhesion conditions. To evaluate pathways potentially involved in hyperoxia-induced growth arrest, we measured extracellular regulated kinase and retinoblastoma protein activation and p21Cip1 and p53 accumulation. Hyperoxia strongly induced activation of extracellular regulated kinase and retinoblastoma protein as well as up-regulation of p21Cip1. These effects of hyperoxia were attenuated under low adhesion conditions, suggesting a role for integrin-dependent signaling. The induction of p21Cip1 and activation of retinoblastoma protein occurred via a p53-independent mechanism. These results suggest that adhesion-dependent pathways are required for hyperoxia-induced cell cycle arrest in macrophages.

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