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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-01-07

AUTHORS

Kenta Torigoe, Yoko Obata, Miki Torigoe, Satoru Oka, Kazuo Yamamoto, Takehiko Koji, Hiroshi Ueda, Hiroshi Mukae, Tomoya Nishino

ABSTRACT

BackgroundProthymosin 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.MethodsCultured 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.ResultsIn 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.ConclusionTaken 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. More... »

PAGES

411-419

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10157-019-01843-1

DOI

http://dx.doi.org/10.1007/s10157-019-01843-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1123949143

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/31912273


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83 nuclear proteins
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86 pretreatment
87 preventative drugs
88 previous studies
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90 protein
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93 renal damage
94 renal tubular cell injury
95 renoprotective effects
96 retinal ischemia
97 serum creatinine
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102 types
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