Abstract
Berberine (BBR) has been demonstrated to protect against renal ischemia/reperfusion injury; however, the underlying molecular mechanism is largely unknown. In the present study, we examined the role of silent information regulator 1 (Sirt1)/p53 in the protective effect of BBR on hypoxia/reoxygenation (H/R)-mediated mitochondrial dysfunction in rat renal tubular epithelial cells (NRK-52E cells). NRK-52E cells were preconditioned with small interfering RNA targeting Sirt1 (Sirt1-siRNA) and BBR before subjected to H/R. Cell damage was assessed by CCK8 assay and detection of oxidative parameters. The apoptotic rate was determined by flow cytometry and Hoechst 33258 staining. The expression of apoptotic markers, Sirt1, p53 and the translocation of p53 were examined by Western blotting assay. Nuclear p53 deacetylation by Sirt1 was detected using immunoprecipitation. Compared with the H/R group, BBR pretreatment increased cell viability and inhibited mitochondrial oxidative stress and apoptosis. Protein expression of Sirt1 was also enhanced along with a reduction of p53. Furthermore, both nuclear translocation of p53 and its acetylation were inhibited in NRK-52E cells pretreated with BBR. However, the knockdown of Sirt1 counteracted the renoprotection of BBR. BBR preconditioning protects rat renal tubular epithelial cells against H/R-induced mitochondrial dysfunction via regulating the Sirt1/p53 pathway.
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Acknowledgements
This work was supported by the Science and Technology Foundation of Tianjin Health Bureau (16KG101, 13KG105), the Natural Science Foundation of China (81700569, 81700659), the Natural Science Foundation of Tianjin (17JCYBJC28000) and the Integrated Western and Chinese Science Foundation of Tianjin Health Bureau (2017056).
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LYB: principal investigator, writing of the protocol, institutional review board submission, data collection, and writing the manuscript; SMW: data collection and analysis, study design and method, final review of data analysis, principal bio-statistician of the project; DYJ and ZN: writing the protocol, data review; SYY and DHY: study design review, monitor scientific process, maintaining patient confidentiality; YWL and LN: corresponding author, scientific advisor, study design, protocol review.
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Lin, Y., Sheng, M., Ding, Y. et al. Berberine protects renal tubular cells against hypoxia/reoxygenation injury via the Sirt1/p53 pathway. J Nat Med 72, 715–723 (2018). https://doi.org/10.1007/s11418-018-1210-1
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DOI: https://doi.org/10.1007/s11418-018-1210-1