Abstract: Objective To clarify the role of hypoxia inducible factor(HIF)-1α in the process of hypoxia-induced cell death through inhibiting its transcription activity. Methods 1 PC12 cells were seeded in the 12-well plate and treated for 24 h in normoxia(20% O₂) or hypoxia(3% O₂). Then photomicrographs under light microscope were taken and analyzed for situation of cell growth by cell-counting method. 2 PC12 cells were seeded in 96-well plate and treated for 24 h in 20% O₂ or 3% O₂. A test for cell survival called MTS was further used to detect the cell viability of PC12 cells. 3 PC12 cells were treated with HIF-1α inhibitor-echinomycin for 24 h or 48 h at 5 nmol/L, 50 nmol/L and 500 nmol/L, respectively. Then MTS was used to detect the cell viability. Results 1 3% O₂ induced the death of PC12 cells significantly contrary to 20% O₂. 2 Echinomycin administration eliminated the cell survival difference between 20% O₂ and 3% O₂ at 24 h. 3 After a 48 h-treatment with echinomycin, it even reversed the hypoxia-enhanced cell death relative to normoxia. Conclusion Hypoxia could promote the death of PC 12 cells. After we used HIF-1α inhibitor echinomycin for 24 h, the death-promotion role of hypoxia was weakened. It even reversed the hypoxia-enhanced cell death after a 48 h-treatment with echinomycin. All these data suggested that the excessive transcription activation during hypoxia was detrimental to PC 12 cells.

Key words: hypoxia, hypoxia inducible factor-1α, PC12 cells, echinomycin