Dose-specific effect of simvastatin on hypoxia-induced HIF-1α and BACE expression in Alzheimers disease cybrid cells

Abstract

Abstract

Background Alzheimers disease (AD) is associated with vascular risk factors; brain ischemia facilitates the pathogenesis of AD. Recent studies have suggested that the reduction of AD risk with statin was achieved by decreased amyloidogenic amyloid precursor protein.

Methods We used mitochondrial transgenic neuronal cell (cybrid) models to investigate changes in the levels of intracellular hypoxia inducible factor 1α (HIF-1α) and β-site amyloid precursor protein cleaving enzyme (BACE) in the presence of simvastatin. Sporadic AD (SAD) and age-matched control (CTL) cybrids were exposed to 2% O2 and incubated with 1μM or 10μM simvastatin.

Results There was no significant difference between cell survival by 1 or 10μM simvastatin in both SAD and CTL cybrids. In the presence of 1μM simvastatin, intracellular levels of HIF-1α and BACE decreased by 40–70% in SAD, but not CTL cybrids. However, 10μM simvastatin increased HIF-1α and BACE expression in both cybrid models.

Conclusion Our results suggest demonstrate differential dose-dependent effects of simvastatin on HIF-1α and BACE in cultured Alzheimers disease cybrid cells.