Impaired induction of HIF-1α in immortalized mouse embryonic fibroblasts lacking both Psen1 and Psen2. Wild type, Psen1-/- (PS1-/-) and Psen1/Psen2-/- (PS-/-) immortalized fibroblasts were treated with 100 μm cobalt chloride for 4 hours (A) or 2.4 μg/ml of insulin for 6 hours (B). Lysates were prepared and Western blotting was performed using an anti HIF-1α antibody. Lower panels show blots reprobed for β-tubulin. Asterisks (*) indicate lanes that were under loaded based on β-tubulin levels. Note the lowered induction of HIF-1α in the cells lacking both presenilins. Representative blots are shown from experiments that were performed multiple times.