Objective    To investigate the effects of chemical hypoxia preconditioning on hypoxia-induced cell injury

and the roles of HIF-1α

HIF-2α and their target gene product VEGF in chemical hypoxia preconditioning in differentiated SH-SY5Y cells.     Methods    Differentiated SH-SY5Y cells were randomly divided into control group

chemical hypoxic preconditioning group (50 μmol/L CoCl

2

for 3 h

then normal culture for 1 h

and 2% O

2

culture for 28 h) and hypoxia group (the same procedures but without CoCl

2

preconditioning). Western blotting was used to examine the expression of HIF-1α

HIF-2α and VEGF proteins. Cell viability was evaluated by measuring lactate dehydrogenase (LDH) release and MTT assay to determine the protective effects of chemical hypoxia preconditioning.     Results    The expression of HIF-2α and VEGF proteins increased in the preconditioning group as compared with those in the hypoxia group (P0.01); whereas the expression of HIF-1α protein had no difference between the two gropes. The preconditioned cells had a higher survival rate and a lower lactate dehydrogenase leakage.     Conclusion    CoCl

2

preconditioning can protect differentiated SH-SY5Y cells from hypoxia injury. The enhanced VEGF protein level that is mediated

at least in part

by HIF-2α

might be involved in the observed preconditioning effects.