We　have　previously　reported　that　5　copies　of　the　hypoxia　response　element　(H　RE)　can　conditionally　regulate　brain-derived　neurotrophic　factor　gene　expression　under　hypoxic/ischemic　conditions　in　mice.　In　the　present　study,　we　investigated　the　controlled　expression　of　neurotrophin-3　(NT-3)　by　H　RE　under　hypoxic　conditions　and　determined　the　protective　effects　of　conditionally　expressed　NT-3　on　hypoxia-induced　apoptosis　in　PC12　cells.　Five　copies　of　the　HRE　(5HRE)　and　the　simian　virus　40　minimal　promoter　(SV40mp)　were　employed　to　construct　a　cassette,　and　transfer　of　therapeutic　gene,　NT-3,　into　PC12　cells　was　achieved　using　a　retroviral　vector.　Our　results　showed　that　the　retroviral　vector,　pLNC-5HRE-NT3,　was　successfully　constructed　and　transfected　into　PC12　cells.　Compared　with　normal　conditions,　in　which　NT-3　was　expressed　at　low　levels,　the　expression　of　NT-3　significantly　increased　under　hypoxic　conditions　in　5HRE-NT3　transgenic　PC12　cells　(P＜0.05).　By　contrast,　in　NT-3　transgenic　PC12　cells　without　HRE,　we　found　no　significant　difference　in　NT-3　expression　between　the　normoxic　and　hypoxic　groups.　The　conditional　adjustment　of　NT-3　expression　by　5HRE　significantly　reduced　apoptosis　induced　by　hypoxia　in　5HRE-NT3　transgenic　PC12　cells　(P＜0.05)　but　not　in　5HRE-enhanced　green　fluorescent　protein　(EGFP)　transgenic　PC12　cells　and　PC12　cells　without　gene　transfer.　In　addition,　the　hypoxia-induced　upregulation　of　both　p38　and　caspase-3　activities　was　suppressed　in　5HRE-NT3　transgenic　PC12　cells　under　hypoxic　conditions　(P＜0.05).　Taken　together,　these　results　demonstrate　that　5HRE-SV40mp　regulates　NT-3　gene　expression　in　response　to　hypoxia　in　PC12　cells.　The　data　presented　in　this　study　may　prove　useful　in　future　gene　therapy　studies　for　the　treatment　of　ischemic　diseases.