Glucose Starvation-Induced Rapid Death of Nrf1α-Deficient, but Not Nrf2-Deficient, Hepatoma Cells Results from Its Fatal Defects in the Redox Metabolism Reprogramming
The response of Nrf1α-/- cells to glucose starvation. (a) Morphological changes of WT, Nrf1α-/-, and Nrf2-/- cells, which had been subjected to glucose deprivation for 12 h, were observed by microscopy (with an original magnification of 200x). (b) The percentage of their dead cells was calculated after being stained by trypan blue. (c) The apoptosis of glucose-starved cells was analyzed by flow cytometry, after being incubated with Annexin V-FITC and PI. (d) Nrf1α-/- cell viability was determined by incubation for 24 h with q-VD-OPH (10 μM), Necrostatin-1 (100 μM), Ferrostatin-1 (2 μM), or 3-methyladenine (2 mM) in the glucose-free media, each of which was resolved in DMSO as a vehicle. (e) Nrf1α-/- cell survival was recovered from glucose deprivation by being cultured for 24 h in alternative media containing 25 mM of fructose (Fru) or mannose (Man). (f) Morphology of Fru/Man-recovered Nrf1α-/- cells was visualized by microscopy (with an original magnification of 200x).