Urinary ATP Synthase Subunit β Is a Novel Biomarker of Renal Mitochondrial Dysfunction in Acute Kidney Injury.
Urinary ATP Synthase Subunit β Is a Novel Biomarker of Renal Mitochondrial Dysfunction in Acute Kidney Injury.
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尿 ATP 合酶亚基 β 是急性肾损伤中肾线粒体功能障碍的新型生物标志物。
DOI：
10.1093/toxsci/kfv038
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Schnellmann,RickG
中科院分区：
文献类型：
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作者：
Whitaker,RyanM;Korrapati,MidhunC;Stallons,LindseyJ;Jesinkey,SeanR;Arthur,JohnM;Beeson,CraigC;Zhong,Zhi;Schnellmann,RickG
Although the importance of mitochondrial dysfunction in acute kidney injury (AKI) has been documented, noninvasive early biomarkers of mitochondrial damage are needed. We examined urinary ATP synthase subunit β (ATPSβ) as a biomarker of renal mitochondrial dysfunction during AKI. Mice underwent sham surgery or varying degrees (5, 10, or 15 min ischemia) of ischemia/reperfusion (I/R)-induced AKI. Serum creatinine, BUN, and neutrophil gelatinase-associated lipocalin were elevated only in the 15 min I/R group at 24 h. Immunoblot analysis of urinary ATPSβ revealed two bands (full length ∼52 kDa and cleaved ∼25 kDa), both confirmed as ATPSβ by LC-MS/MS, that increased at 24 h in 10- and 15-min I/R groups. These changes were associated with mitochondrial dysfunction evidenced by reduced renal cortical expression of mitochondrial proteins, ATPSβ and COX1, proximal tubular oxygen consumption, and ATP. Furthermore, in the 15-min I/R group, urinary ATPSβ was elevated until 72 h before returning to baseline 144 h after reperfusion with recovery of renal function. Evaluation of urinary ATPSβ in a nonalcoholic steatohepatitis model of liver injury only revealed cleaved ATPSβ, suggesting specificity of full-length ATPSβ for renal injury. Immunoblot analyses of patient urine samples collected 36 h after cardiac surgery revealed increased urinary ATPSβ levels in patients with postcardiac surgery-induced AKI. LC-MS/MS urinalysis in human subjects with AKI confirmed increased ATPSβ. These translational studies provide evidence that ATPSβ may be a novel and sensitive urinary biomarker of renal mitochondrial dysfunction and could serve as valuable tool for the testing of potential therapies for AKI and chemical-induced nephrotoxicity.
