Hypoxia increases glyceraldehyde-3-phosphate dehydrogenase transcription in rat alveolar epithelial cells

Alveolar epithelial type II (ATII) cells are particularly hypoxia-tolerant in vitro. As one of the mechanisms of hypoxia tolerance is the induction of certain proteins, one of which is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we investigated whether hypoxia modified GAPDH expression in ATII cells. Hypoxia induced a time- and O(2) concentration-dependent accumulation of GAPDH mRNA in cultured rat ATII cells (2- to 3-fold the normoxic value after 18 h in 0% O(2)), an effect completely reversed by reoxygenation. GAPDH mRNA induction was accounted for by an increase in GAPDH gene transcription during hypoxia with no change in mRNA stability. GAPDH protein synthesis increased 3- to 4-fold after 18 h of 0% O(2), while the GAPDH protein steady-state level rose by 75%. GAPDH enzymatic activity in hypoxic cell homogenates increased by 45%. These results indicate that hypoxia induces GAPDH expression in ATII cells through an increase in transcription.