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

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.

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.

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.

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.