![PKR activator or GBT021601 reduces 2,3-DPG levels in HbSS RBCs and modulates ATP under normoxia and hypoxia. (A) Under normoxia, HbAA RBCs exhibited higher ATP levels compared to HbSS RBCs (HbAA [n = 5] vs HbSS [n = 27]; ∗P < .05; Mann-Whitney U test). ATP levels in untreated HbSS RBCs were unaffected by treatment with Vox, PKR activator, or GBT021601 (ns, P > .05; Wilcoxon test). (B) Normoxic 2,3-DPG levels were lower in HbAA RBCs than in HbSS RBCs (HbAA, n = 5 vs HbSS, n = 27; ∗P < .05, Mann-Whitney U test). PKR activator and GBT021601 reduced 2,3-DPG levels in HbSS RBCs (HbSS vs HbSS + PKR [n = 27; ∗∗P < .01; Wilcoxon test]; HbSS vs HbSS + GBT021601 [n = 5; ∗∗P < .01; Wilcoxon test]), whereas Vox had no effect (ns, P > .05; Wilcoxon test). (C) Under hypoxia, HbAA RBCs retained higher ATP levels than HbSS RBCs (HbAA [n = 5] vs HbSS [n = 10]; ∗P < .05; Mann-Whitney U test). PKR treatment increased ATP levels (HbSS vs HbSS + PKR; n = 10; ∗∗P < .01; Wilcoxon test), whereas Vox and GBT021601 had no effect (ns; P > .05; Wilcoxon test). (D) Similar to normoxia, hypoxic 2,3-DPG levels were lower in HbAA RBCs compared to HbSS RBCs (HbAA [n = 5] vs HbSS [n = 10]; ∗P < .05; Mann-Whitney U test). PKR activator and GBT021601 reduced 2,3-DPG levels (HbSS vs HbSS + PKR; ∗P < .05; HbSS vs HbSS + GBT021601; ∗P < .05; Wilcoxon test), whereas Vox had no effect (ns, P > .05; Wilcoxon test). Error bars are presented as SEM. ns, not significant.](https://ash.silverchair-cdn.com/ash/content_public/journal/bloodrci/1/2/10.1016_j.brci.2025.100015/3/brci_rci-2025-000108-gr2.jpeg?Expires=1763157816&Signature=bGAlb4qOMTJXGWq1jBcSV-3RXYpA4GemdXe~OmkuRx0Zjum6i9BUXQBNvR~lUB5lZkCHqJ-W~OI5wkOacuff1J9y8o81VdoOlCMkVVgQO1m0t53Zt5CdrNP3d-F2cr7U4BHroxlXBGHMENH8rrWNFtSUuSqfdcJjm2sCkhLk8yV1lQrSdo-sj~-9VJk8JO8NEnAH6JmlETpF5D-~-Ntv1AVEJAHdEl698wX6mIwc0NFSQCPAWRuR2IqOMzK0TmTqh8e4BNJ~6ylNgQg-YLhP32QbJHE2a-zof3-nvjf0Ag~rojFHLcry6lMpG~89ktqI2~PnXqGgdKRenCgAojkDaQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
PKR activator or GBT021601 reduces 2,3-DPG levels in HbSS RBCs and modulates ATP under normoxia and hypoxia. (A) Under normoxia, HbAA RBCs exhibited higher ATP levels compared to HbSS RBCs (HbAA [n = 5] vs HbSS [n = 27]; ∗P < .05; Mann-Whitney U test). ATP levels in untreated HbSS RBCs were unaffected by treatment with Vox, PKR activator, or GBT021601 (ns, P > .05; Wilcoxon test). (B) Normoxic 2,3-DPG levels were lower in HbAA RBCs than in HbSS RBCs (HbAA, n = 5 vs HbSS, n = 27; ∗P < .05, Mann-Whitney U test). PKR activator and GBT021601 reduced 2,3-DPG levels in HbSS RBCs (HbSS vs HbSS + PKR [n = 27; ∗∗P < .01; Wilcoxon test]; HbSS vs HbSS + GBT021601 [n = 5; ∗∗P < .01; Wilcoxon test]), whereas Vox had no effect (ns, P > .05; Wilcoxon test). (C) Under hypoxia, HbAA RBCs retained higher ATP levels than HbSS RBCs (HbAA [n = 5] vs HbSS [n = 10]; ∗P < .05; Mann-Whitney U test). PKR treatment increased ATP levels (HbSS vs HbSS + PKR; n = 10; ∗∗P < .01; Wilcoxon test), whereas Vox and GBT021601 had no effect (ns; P > .05; Wilcoxon test). (D) Similar to normoxia, hypoxic 2,3-DPG levels were lower in HbAA RBCs compared to HbSS RBCs (HbAA [n = 5] vs HbSS [n = 10]; ∗P < .05; Mann-Whitney U test). PKR activator and GBT021601 reduced 2,3-DPG levels (HbSS vs HbSS + PKR; ∗P < .05; HbSS vs HbSS + GBT021601; ∗P < .05; Wilcoxon test), whereas Vox had no effect (ns, P > .05; Wilcoxon test). Error bars are presented as SEM. ns, not significant.
