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International Urology and Nephrology
Erschienen in: International Urology and Nephrology 8/2023

10.06.2023 | Urology - Original Paper

Sufentanil inhibits Pin1 to attenuate renal tubular epithelial cell ischemia–reperfusion injury by activating the PI3K/AKT/FOXO1 pathway

verfasst von: Chunhui Liu, Qingdong Wang, Li Niu

Erschienen in: International Urology and Nephrology | Ausgabe 8/2023

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Abstract

Background

Renal ischemia–reperfusion injury (RIRI) has become a great concern in clinical practice with high morbidity and mortality rates. Sufentanil has protective effects on IRI-induced organ injury. Herein, the effects of sufentanil on RIRI were investigated.

Methods

RIRI cell model was established by hypoxia/reperfusion (H/R) stimulation. The mRNA and protein expressions were assessed using qRT-PCR and western blot. TMCK-1 cell viability and apoptosis were assessed using MTT assay and flow cytometry, respectively. The mitochondrial membrane potential and ROS level were detected by JC-1 mitochondrial membrane potential fluorescent probe and DCFH-DA fluorescent probe, respectively. LDH, SOD, CAT, GSH and MDA levels were determined by the kits. The interaction between FOXO1 and Pin1 promoter was analyzed using dual luciferase reporter gene and ChIP assays.

Results

Our results revealed that sufentanil treatment attenuated H/R-induced cell apoptosis, mitochondrial membrane potential (MMP) dysfunction, oxidative stress, inflammation and activated PI3K/AKT/FOXO1 associated proteins, while these effects were reversed by PI3K inhibitor, suggesting that sufentanil attenuated RIRI via activating the PI3K/AKT/FOXO1 signaling pathway. We subsequently found that FOXO1 transcriptionally activated Pin1 in TCMK-1 cells. Pin1 inhibition ameliorated H/R-induced TCMK-1 cell apoptosis, oxidative stress and inflammation. In addition, as expected, the biological effects of sufentanil on H/R-treated TMCK-1 cells were abrogated by Pin1 overexpression.

Conclusion

Sufentanil reduced Pin1 expression through activation of the PI3K/AKT/FOXO1 signaling to suppress cell apoptosis, oxidative stress and inflammation in renal tubular epithelial cells during RIRI development.
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Metadaten
Titel
Sufentanil inhibits Pin1 to attenuate renal tubular epithelial cell ischemia–reperfusion injury by activating the PI3K/AKT/FOXO1 pathway
verfasst von
Chunhui Liu
Qingdong Wang
Li Niu
Publikationsdatum
10.06.2023
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 8/2023
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-023-03651-9

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