Hexapeptide derived from prothymosin alpha attenuates cisplatin-induced acute kidney injury.
Hexapeptide derived from prothymosin alpha attenuates cisplatin-induced acute kidney injury.
复制标题
源自胸腺肽α原的六肽可减轻顺铂引起的急性肾损伤。
DOI：
10.1007/s10157-019-01843-1
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发表时间：
2020
期刊：
影响因子：
2.3
通讯作者：
Nishino T
中科院分区：
文献类型：
--
作者：
Torigoe K;Obata Y;Torigoe M;Oka S;Yamamoto K;Koji T;Ueda H;Mukae H;Nishino T
研究背景胸腺素原α（ProTα）是一种在哺乳动物组织中表达的核蛋白。先前的研究表明，ProTα在各种细胞类型中表现出对缺血诱导的细胞死亡的保护作用。最近，6-残基肽P6 Q（NEVDQE），即ProTα中活性6-残基核心（51-56）的修饰形式，也已被证明对视网膜缺血具有保护作用。然而，P6 Q是否对急性肾损伤（阿基）有效仍有待阐明。方法培养的HK-2细胞经顺铂处理24 h后，再用ProTα或P6 Q预处理30 min，MTT法检测细胞活力。在体内研究中，将8周龄雄性Wistar大鼠分为对照组、顺铂治疗组和顺铂治疗P6 Q注射组。在最后一组中，在顺铂治疗前静脉注射P6 Q。结果在体外培养的细胞研究中，ProTα或P6 Q预处理可阻止顺铂诱导的细胞死亡。在体内研究中，P6 Q预处理显著减弱顺铂诱导的血清肌酐和血尿素氮水平升高、肾小管细胞损伤和细胞凋亡。此外，P6 Q衰减线粒体凋亡途径和加速Akt磷酸化后顺铂诱导的肾damage. ConclusionTowards，我们的研究结果表明，P6 Q可以减弱顺铂诱导的阿基和抑制线粒体凋亡途径通过Akt磷酸化。这些数据表明，P6 Q具有作为顺铂诱导的阿基的预防药物的潜力。
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.