The effect of baseline O < sub > 2 < /sub > conditions on the response of prostate cancer cells to hypoxia

Am J Physiol Cell Physiol. 2024 Apr 22. doi: 10.1152/ajpcell.00155.2024. Online ahead of print.ABSTRACTThe transcriptional response to hypoxia is largely regulated by the hypoxia-inducible factors (HIFs), which induce the expression of genes involved in glycolysis, angiogenesis, proliferation, and migration. Virtually all cell culture-based hypoxia experiments have used near-atmospheric (18% O2) oxygen levels as baseline for comparison to hypoxia. However, this is hyperoxic compared to mammalian tissue microenvironments, where oxygen levels range from 2-9% O2 (physioxia). Thus, these experiments actually compare hyperoxia to hypoxia. To determine how the baseline O2 level affects the subsequent response to hypoxia, we cultured PC-3 prostate cancer cells in either 18% or 5% O2 for two weeks prior to exposing them to hypoxia (~1.1% pericellular O2) for 12-48 h. RNA-seq revealed that the transcriptional response to hypoxia was dependent on the baseline O2 level. Cells grown in 18% O2 prior to hypoxia exposure showed an enhanced induction of HIF targets, particularly genes involved in glucose metabolism, compared to cells grown in physioxia prior to hypoxia. Consistent with this, hypoxia significantly increased glucose consumption and metabolic activity only in cells previously cultured in 18% O2, but not in cells preadapted to 5% O2. Transcriptomic analyses also indicated effects on cell proliferation and motility, which were followed up by functional assays. While unaffected by...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Source Type: research