A reduced-oxygen environment elicits a rapid, transient Bcl-x_L induction and a slower, persistent Bim suppression. (A-I) Mice were placed in a low oxygen chamber (11%) on day 0, for up to 5 days. (A) Endogenous plasma Epo, assayed by ELISA. Data are mean ± SEM. Epo was significantly elevated relative to day 0 (n = 27 mice) on all subsequent days (n = 6 to 12 mice per time point, P < .006, 2-tailed t test, unequal variance). The Epo time course is redrawn in gray in panels E to I. (B) Daily hematocrit (HCT) of blood collected immediately after euthanasia. Data are mean ± SEM of n ≥ 6 mice per time point. Differences from day 0 were significant at 12 hours (P = .019), 18 hours to day 5 (P < .0002). (C-D) Spleen ProE and EryA (cell number per gram body weight). Data pooled from 23 independent experiments. Each data point is mean ± SEM of n ≥ 6 mice. Differences from day 0 (n = 82 mice) were significant for ProE on day 1 (P = .005), day 2 (P = .047), days 3 to 5 (P ≤ .005), and for EryA on day 2 (P = .034), days 3 to 5 (P ≤ .001). (E) Annexin V binding in spleen ProE (blue) and EryA (black). Data points are mean ± SEM of 33 mice for day 0, and 3 to 7 mice for subsequent days, pooled from 2 to 5 independent experiments per day. Differences from day 0 are significant for ProE on days 3 to 5 (P ≤ .002), and for EryA on day 1 (P = .001) and days 3 to 5 (P = .03, 0.02, 0.001, respectively). (F) Fas-positive cell frequency in spleen ProE (blue) and EryA (black), measured by flow cytometry in freshly explanted tissue. Data are mean ± SEM of n = 26 mice pooled from 4 experiments (day 0), or n = 3 mice for subsequent days. Differences from day 0 were significant for ProE on day 1 (P = .024), day 3 (P < .00001), day 5 (P = .001), and for EryA on day 5 (P = .04). (G) Bcl-x_L protein in spleen ProE and EryA measured by flow cytometry in freshly explanted tissue. Data pooled from 3 independent experiments. Each data point is mean ± SEM of n ≥ 3 mice. Differences from day 0 (n = 17) are significant for ProE at 18 hours (n = 3, P < .001), 24 hours (n = 7, P = .019), 48 hours (n = 5, P < .0005), and for EryA, at 12 hours (P = .046), 18 hours (P < .0001), 48 hours (P = .02). (H-I) Bim protein expression in spleen (H) and BM (I) ProE and EryA, measured by flow cytometry in freshly explanted tissue. Data are mean ± SEM of n ≥ 3 mice. Differences from day 0 were significant for spleen ProE on day 1 (P = .014), days 3 to 5 (P ≤ .005), spleen EryA on day 0.5 (P = .0014), days 2 to 5 (P < .04), BM ProE on day 2 (P = .007), day 3 (P < .00001), day 4 (P < .001), day 5 (P = .04), BM EryA on day 1 (P = .002), day 2 (P = .0001), day 3 (P = .05).