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Berberine protects HK-2 cells from hypoxia/reoxygenation induced apoptosis via inhibiting SPHK1 expression

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Abstract

Renal ischemia reperfusion injury (RIRI) refers to the irreversible damage for renal function when blood perfusion is recovered after ischemia for an extended period, which is common in clinical surgeries and has been regarded as a major risk for acute renal failures (ARF) that is accompanied with unimaginably high morbidity and mortality. Hypoxia during ischemia followed by reoxygenation via reperfusion serves as a major event contributing to cell apoptosis, which has been widely accepted as the vital pathogenesis in RIRI. Preventing apoptosis in renal tubular epithelial cell has been considered as effective method for blocking RIRI. In this paper, we established a hypoxia/reoxygenation (H/R) injury model in human proximal tubular epithelial HK-2 cells. Here, we found increased SPHK1 levels in H/R injured HK-2 cells, which could be significantly down regulated after berberine treatment. Berberine has been reported to exert a protective effect on H/R-induced apoptosis of HK-2 cells. So, in our present study, we planned to investigate whether SPHK1 participated in the anti-apoptosis process of berberine in H/R injured HK-2 cells. Our study confirmed the protective effect of berberine against H/R-induced apoptosis in HK-2 cells through promoting cells viability, inhibiting cells apoptosis, and down-regulating p-P38, caspase-3, caspase-9 as well as SPHK1, while up regulating the ratio of Bcl-2/Bax. However, SPHK1 overexpression in HK-2 cells induced severe apoptosis, which can be significantly ameliorated with additional berberine treatment. We concluded that berberine could remarkably prevent H/R-induced apoptosis in HK-2 cells through down-regulating SPHK1 expression levels, and the mechanisms included the suppression of p38 MAPK activation and mitochondrial stress pathways.

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Acknowledgements

The study was supported by the grant 15401930600 from Shanghai Science and Technology Committee.

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Author notes

  1. Jianrao Lu and Yang Yi contributed to this work equally.

Authors and Affiliations

  1. Department of Nephrology, Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China

    Jianrao Lu, Chuanfu Zhang, Haiyan Han, Jie Chen & Wenrui Liu

  2. Department of Nephrology, Jingan District Central Hospital/Jingan Branch, Huashan Hospital affiliated to Fudan University, Shanghai, 200040, China

    Yang Yi

  3. Department of Nephrology, Liyang Hospital of traditional Chinese medicine, Jiangsu Province, 213300, China

    Ronghua Pan

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  1. Jianrao Lu
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  2. Yang Yi
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  3. Ronghua Pan
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  4. Chuanfu Zhang
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  5. Haiyan Han
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  6. Jie Chen
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Correspondence to Jianrao Lu or Ronghua Pan.

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Lu, J., Yi, Y., Pan, R. et al. Berberine protects HK-2 cells from hypoxia/reoxygenation induced apoptosis via inhibiting SPHK1 expression. J Nat Med 72, 390–398 (2018). https://doi.org/10.1007/s11418-017-1152-z

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  • DOI: https://doi.org/10.1007/s11418-017-1152-z

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