| First Author | Zhang W | Year | 2017 |
| Journal | Neuroscience | Volume | 366 |
| Pages | 95-104 | PubMed ID | 28951325 |
| Mgi Jnum | J:258118 | Mgi Id | MGI:6121282 |
| Doi | 10.1016/j.neuroscience.2017.09.035 | Citation | Zhang W, et al. (2017) Sirtuin 6 protects the brain from cerebral ischemia/reperfusion injury through NRF2 activation. Neuroscience 366:95-104 |
| abstractText | Sirtuin 6 (SIRT6), a member of the sirtuin family of NAD(+)-dependent deacetylases, has been shown to produce beneficial effects in myocardial ischemia/reperfusion (I/R). However, the role of SIRT6 in cerebral I/R is largely unclear. In this study, we investigated the effects of SIRT6 overexpression in regulating I/R injury in a mouse cerebral I/R model in vivo and in oxygen-glucose-deprivation/reoxygenation (OGD/R)-stimulated neuro-2a neuroblastoma cells in vitro. We found that cerebral I/R (1h/24h) resulted in decreased SIRT6 expression in the cerebral cortex (P<0.01). SIRT6 overexpression in the brain by in vivo gene transfer enhanced the antioxidant NRF2 signaling (P<0.05), reduced oxidative stress (P<0.05), and attenuated cerebral I/R-induced brain tissue damage and neurological deficits (P<0.05). These neuroprotective effects of SIRT6 overexpression were abolished in NRF2 knockout mice. In neuro-2A neuroblastoma cells, SIRT6 overexpression increased total and nuclear NRF2 levels (P<0.05), reduced oxidative stress (P<0.05), and attenuated OGD/R-induced cell death (P<0.05); these protective effects were blocked by NRF2 knockdown (P<0.05). Moreover, in OGD/R-stimulated neuro-2A cells, SIRT6 overexpression produced similar protective effects to those induced by the antioxidant NAC, but no added benefits were detected when SIRT6 overexpression was used in combination with NAC (P>0.05). These findings provide evidence that SIRT6 can protect the brain from cerebral I/R injury by suppressing oxidative stress via NRF2 activation. Thus, SIRT6 may serve as a potential therapeutic target for ischemic stroke. |
