Reperfusion syndrome: state of the art

Matveev, D V; Kuznetsov, M R; Matveev, A D; Evteev, A V; Fedorov, E E

doi:10.33529/angio2020421

Cited by 7 publications

(1 citation statement)

References 41 publications

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“…During ischemic stroke, a series of harmful cascades occur, including oxidative stress and an inflammatory response, which may eventually result in apoptosis ( 5 ). To date, the restoration of blood reperfusion and the resupply of nutrients remain the most efficient treatments for stroke ( 6 ). However, cerebral ischemia/reperfusion (CI/R) injury presents a serious complication, which complicates therapy for ischemic stroke patients ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

TGR5 overexpression mediated by the inhibition of transcription factor SOX9 protects against hypoxia-/reoxygenation-induced injury in hippocampal neurons by activating Nrf2/HO-1 signaling

Jia¹,

Chen²,

Liu³

2022

Ann Transl Med

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Background: Cerebral ischemia/reperfusion (CI/R) injury is a destructive cerebrovascular disease associated with long-term disability and high mortality rates. TGR5 has been discovered in multiple human and animal tissues and to modulate a variety of physiological processes. The current study sought to reveal the function of TGR5 in CI/R injury and uncover the latent regulatory mechanism.Methods: A hypoxia/reoxygenation (H/R) model was established in mouse hippocampal HT22 cells.The TGR5 expression in the H/R-treated HT22 cells was tested by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blots. After TGR5 was overexpressed, Cell Counting Kit-8 assays were used to estimate cell viability, and lactate dehydrogenase (LDH) release was assessed by a LDH assay kit. Cell apoptosis was measured by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assays. Cytochrome c release was detected by immunofluorescence assays and western blots were used to analyze the protein levels of apoptosis-related factors. The oxidative stress levels were assessed by corresponding kits. Next, SOX9 expression in the H/R-treated HT22 cells was tested by RT-qPCR and western blots. The interaction between the TGR5 promoter and SOX9 was verified by luciferase reporter and chromatin immunoprecipitation assays. Subsequently, after the H/R-treated HT22 cells had been cotransfected with TGR5 overexpression and SOX9 overexpression plasmids, TGR5 expression was tested by RT-qPCR and western blots, and the above-mentioned functional experiments were repeated. Finally, the expression of Nrf2/HO-1 signaling-related proteins was examined by western blots.Results: TGR5 expression was significantly decreased in the H/R-exposed HT22 cells. The elevation of TGR5 enhanced the viability, hindered the apoptosis, and alleviated the oxidative stress of the HT22 cells under H/R conditions. Additionally, SOX9 had a strong affinity with TGR5 promoter, and TGR5 was transcriptionally inhibited by SOX9. Further, SOX9 overexpression restored the protective role of TGR5 upregulation in H/R-induced HT22 cell injury. Additionally, TGR5 overexpression mediated by SOX9 inhibition activated Nrf2/HO-1 signaling.Conclusions: TGR5 was transcriptionally inhibited by SOX9, and the overexpression of TGR5 played a protective role in CI/R injury.

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Section: Introductionmentioning

confidence: 99%