Stabilization of hypoxia-inducible factor 2α (HIF-2α) impairs acute galactose-induced redox coupling and cell viability. Chondrocytes were cultured in glucose- or galactose-supplemented media for 1 or 5 days and were treated with cobalt chloride (CoCl2) for the final 24 hours to evaluate the effect of acute stabilization of HIF-2α. (A) CoCl2-mediated HIF-2α stabilization after 1 day of culture prevented the galactose-induced reduction in superoxide dismutase 2 (SOD2) expression but had no effect on expression at 5 days or in any glucose culture condition (n = 3). (B) CoCl2 treatment reduced succinate dehydrogenase (SDH) expression in 1-day glucose cultured cells and showed a trend for reduced expression in galactose-treated samples at 1 and 5 days. Notably, CoCl2 treatment prevented the upregulation in SDH expression after 5 days of galactose culture (n = 3). (C) HIF-2α stabilization reduced cell viability in galactose- but not glucose-treated chondrocytes during the acute (1 day) response to galactose (n = 3). After 5 days in glucose or galactose culture, HIF-2α stabilization modestly reduced cell viability in glucose-treated cells, with a trend for reduced viability after galactose treatment (n = 6). Bars represent mean ± standard error of the mean. *P <0.05 between +/− CoCl2 treatment.