Abstract
Background Astrocytes mediate brain defense against oxidative stress-induced injury. Silent information regulator 1 (SIRT1) has anti-oxidative stress effects in many diseases and is highly expressed in astrocytes. However, the neuroprotective effects of SIRT1 on astrocytes after cerebral ischemia/reperfusion injury are unclear. Methods Here, we evaluated the effects of SIRT1 in astrocytes after cerebral ischemia/reperfusion injury using oxygen-glucose deprivation/recovery in astrocytes in vitro and middle cerebral artery occlusion in rats in vivo. Results SIRT1 knockdown reduced cell viability, increased oxidative stress, and decreased peroxisome proliferator activated receptor (PPAR)-γ coactivator (PGC)-1α, PPARγ, nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase (HO)-1, and NAD(P)H:quinone oxidoreductase-1 (NQO1) expression. Moreover, SIRT1 knockdown also suppressed PGC-1α activity, the PGC-1α/PPARγ interaction, and the PPARγ/peroxisome proliferator-response element (PPRE) interaction. Similarly, in our in vivo experiments, SIRT1 overexpression and PGC-1α or PPARγ knockdown reduced PGC-1α, PPARγ, NRF2, HO-1, and NQO1 protein expression and blocked the PGC-1α/PPARγ interaction. SIRT1 overexpression plus PPARγ knockdown inhibited the interaction of PPARγ with PPRE. NRF2 knockdown blocked NRF2 expression and downstream proteins induced by SIRT1 overexpression. Conclusion Overall, our data indicated that SIRT1 directly mediated the PGC-1α/PPARγ pathway in response to focal cerebral ischemia/reperfusion-induced neurological deficit, providing insights into the treatment of focal cerebral ischemia/reperfusion injury.
Coicis semen protects against focal cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting angiogenesis via the TGFβ/ALK1/Smad1/5 signaling pathway