Hypoxia and reoxygenation increased BACE1 mRNA and protein levels in human neuroblastoma SH-SY5Y cells

Ischemic cerebrovascular diseases, usually involved in hypoxia and reoxygenation, have been reported to increase the risk of dementia such as Alzheimer's disease (AD). β-site amyloid protein precursor (APP)-cleaving enzymes (BACE1) have been identified to participate in the secretion of β-amyloid peptides (Aβ), and its expressive alteration would contribute to the AD neuropathology. We have investigated the effect of hypoxia (0% O₂, 24 h) and reoxygenation (0 h, 12 h and 24 h after 24 h hypoxia) on BACE1 mRNA and protein levels in human neuroblastoma SH-SY5Y cells. At the same time, we also examined the effect of hypoxia and reoxygenation on APP mRNA and protein levels. We demonstrated that hypoxia and reoxygenation did not alter APP mRNA and protein level, However compared to those of controls, BACE1 mRNA levels were up-regulated by 31.5% (P = 0.028) and 35.1% (P = 0.005) at 12 h and 24 h and the protein levels increased to 22%(P = 0.021), 42% (P = 0.000) and 51.5% (P = 0.000) at 0 h, 12 h and 24 h after reoxygenation, respectively. Thus by up-regulating of BACE1 mRNA and protein level in the neuronal cell, hypoxia may be a linkage in the pathophysiology between cerebravascular diseases and AD.