Growth arrest in A549 cells during hyperoxic stress is associated with decreased cyclin B1 and increased p21Waf1/Cip1/Sdi1 levels

Sharon A. McGrath-Morrow, Jennifer Stahl

Research output: Contribution to journalArticlepeer-review

Abstract

Exposure to high concentrations of oxygen has previously been shown to cause growth arrest in A549 cells, a distal lung epithelial cell line. We found that when A549 cells were exposed to 95% oxygen they underwent substantial growth inhibition. This was associated with induction of p21Waf1/Cip1/Sdi1 protein and a decrease in cyclin B1 protein. Flow cytometry revealed that A549 cells exposed to hyperoxia had a significant decrease in the percentage of cells in G1 and a modest but significant increase in the percentage of cells in S phase and G2/M, consistent with cells entering S phase. A549 cells in room air and hyperoxia were then treated with nocodazole, a mitotic inhibitor. Room air A549 cells treated with nocodazole showed a marked increase in G2/M consistent with mitotic arrest. In contrast, hyperoxic treated cells had a modest but significant decrease in G1 but only a minimal increase in G2/M consistent with partial G1/S arrest and growth inhibition in S phase. To further investigate the role of p21Waf1/Cip1/Sdi1 as a checkpoint regulator during hyperoxic growth inhibition, HCT116 cells with wild-type and null p21Waf1/Cip1/Sdi1 were exposed to hyperoxia. Both wild-type p21(+/+) cells and null p21(-/-) cells underwent growth inhibition when exposed to hyperoxia. At 48 h the hyperoxic treated HCT116 p21(+/+) had a similar cell cycle distribution as the hyperoxic treated HCT116 p21(-/-) cells, suggesting that p21Waf1/Cip1/Sdi1 may not be essential for growth arrest during hyperoxia. These findings suggest that hyperoxia causes partial growth arrest at different phases of the cell cycle but primarily in S phase, that hyperoxic growth arrest is associated with a decrease in cyclin B1 protein and that p21 induction may not be essential for hyperoxic growth arrest.

Original languageEnglish (US)
Pages (from-to)90-97
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1538
Issue number1
DOIs
StatePublished - Feb 5 2001

Keywords

  • A549 cell
  • Hyperoxia
  • p21

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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