SIRT1 Inhibits High Shear Stress-Induced Apoptosis in Rat Cortical Neurons.

INTRODUCTION: Sirtuin1 (SIRT1), one of NAD+-dependent protein deacetylases, is proved to be neuroprotective in aging diseases, but its effect on neuronal apoptosis has not been clarified. To investigate the role of SIRT1 in inhibiting neuronal apoptosis, SIRT1 was interfered or overexpressed in cortical neurons. METHODS: We exerted overloading laminar shear stress with 10 dyn/cm2 for 4, 8, and 12 h on neurons to cause cortical neuronal apoptosis, and the apoptosis percentage was tested by TUNEL assay. The adenovirus plasmids containing SIRT1 RNA interference or SIRT1 wild type gene were transfected into neurons before shear stress loading. SIRT1 mRNA and protein level were tested by Real-time PCR, immunofluorescence and western blots assay. RESULTS: SIRT1 was primarily expressed in nucleus of cortical neurons, and its mRNA level was significantly increased after 4 h stimulation. SIRT1 RNAi cortical neurons had higher TUNEL positive cells, while SIRT1 overexpression significantly decreased the percentage of died cells induced by shear stress compared to control group. CONCLUSIONS: SIRT1 plays a neuroprotective role in shear stress induced apoptosis and could be as potential pharmacological targets against neuronal degeneration in future.