WITHDRAWN: Silent information regulator 1 ameliorates oxidative stress injury via PGC-1α/PPARγ-Nrf2 pathway after ischemic stroke in rat.

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.

Novel insights into autophagy in gastrointestinal pathologies, mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

“…The other paper of significance in the current issue of the World Journal of Gastroenterology , acknowledged by us, is the original paper by Zhou et al [ 15 ].…”

“…The study by Zhou et al [ 15 ] used mainly mouse and cell models but not clinical settings. Although their research demonstrated reduced expression of SIRT1 in human ALF liver tissue, the effectiveness of SIRT1 activators in treating acute liver injury and failure remains uncertain.…”