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Hexapeptide derived from prothymosin alpha attenuates cisplatin-induced acute kidney injury

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Abstract

Background

Prothymosin alpha (ProTα) is a nuclear protein expressed in virtually all mammalian tissues. Previous studies have shown that ProTα exhibits protective effects against ischemia-induced cell death in various cell types. Recently, the 6-residue peptide P6Q (NEVDQE), the modified form of the active 6-residue core (51–56) in ProTα, has also been shown to have protective effects against retinal ischemia. However, it remains to be elucidated whether P6Q is effective against acute kidney injury (AKI). Therefore, we investigated the renoprotective effect of P6Q on cisplatin-induced AKI.

Methods

Cultured HK-2 cells were treated with cisplatin for 24 h and pretreatment with ProTα or P6Q was carried out 30 min before cisplatin treatment. Cell viability was evaluated using the MTT assay. In an in vivo study, 8-week-old male Wistar rats were divided into control, cisplatin treated, and cisplatin treated with P6Q injection groups. In the last of these, P6Q was injected intravenously before cisplatin treatment. Then, we evaluated the renoprotective effect of P6Q.

Results

In the study on cultured cells, pretreatment with ProTα or P6Q prevented cisplatin-induced cell death. In the in vivo study, pretreatment with P6Q significantly attenuated cisplatin-induced increase in serum creatinine and blood urea nitrogen levels, renal tubular cell injury, and apoptosis. Moreover, P6Q attenuated the mitochondrial apoptotic pathway and accelerated Akt phosphorylation after cisplatin-induced renal damage.

Conclusion

Taken together, our findings indicate that P6Q can attenuate cisplatin-induced AKI and suppress the mitochondrial apoptotic pathway via Akt phosphorylation. These data suggest that P6Q has potential as a preventative drug for cisplatin-induced AKI.

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Acknowledgements

We thank Ms. Ryoko Yamamoto for excellent experimental assistance.

Funding

This research received no specific grant from any funding agency.

Author information

Authors and Affiliations

  1. Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Kenta Torigoe, Yoko Obata, Miki Torigoe, Satoru Oka & Tomoya Nishino

  2. Medical Educational Development Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Yoko Obata

  3. Biomedical Research Support Center, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Kazuo Yamamoto

  4. Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Takehiko Koji

  5. Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan

    Hiroshi Ueda

  6. Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Hiroshi Mukae

Authors
  1. Kenta Torigoe
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  2. Yoko Obata
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  6. Takehiko Koji
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  7. Hiroshi Ueda
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  8. Hiroshi Mukae
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  9. Tomoya Nishino
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Correspondence to Yoko Obata.

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This article does not contain any studies with human participants.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (IRB approval number 1506261242-5).

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Torigoe, K., Obata, Y., Torigoe, M. et al. Hexapeptide derived from prothymosin alpha attenuates cisplatin-induced acute kidney injury. Clin Exp Nephrol 24, 411–419 (2020). https://doi.org/10.1007/s10157-019-01843-1

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  • DOI: https://doi.org/10.1007/s10157-019-01843-1

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