Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice

Ana Andres-Hernando, Nanxing Li, Christina Cicerchi, Shinichiro Inaba, Wei Chen, Carlos Roncal-Jimenez, Myphuong T. Le, Michael F. Wempe, Tamara Milagres, Takuji Ishimoto, Mehdi Fini, Takahiko Nakagawa, Richard J. Johnson and Miguel A. Lanaspa ()
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Ana Andres-Hernando: University of Colorado Denver
Nanxing Li: University of Colorado Denver
Christina Cicerchi: University of Colorado Denver
Shinichiro Inaba: University of Colorado Denver
Wei Chen: University of Colorado Denver
Carlos Roncal-Jimenez: University of Colorado Denver
Myphuong T. Le: University of Colorado Denver
Michael F. Wempe: University of Colorado Denver
Tamara Milagres: University of Colorado Denver
Takuji Ishimoto: University of Colorado Denver
Mehdi Fini: University of Colorado Denver
Takahiko Nakagawa: University of Colorado Denver
Richard J. Johnson: University of Colorado Denver
Miguel A. Lanaspa: University of Colorado Denver

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Acute kidney injury is associated with high mortality, especially in intensive care unit patients. The polyol pathway is a metabolic route able to convert glucose into fructose. Here we show the detrimental role of endogenous fructose production by the polyol pathway and its metabolism through fructokinase in the pathogenesis of ischaemic acute kidney injury (iAKI). Consistent with elevated urinary fructose in AKI patients, mice undergoing iAKI show significant polyol pathway activation in the kidney cortex characterized by high levels of aldose reductase, sorbitol and endogenous fructose. Wild type but not fructokinase knockout animals demonstrate severe kidney injury associated with ATP depletion, elevated uric acid, oxidative stress and inflammation. Interestingly, both the renal injury and dysfunction in wild-type mice undergoing iAKI is significantly ameliorated when exposed to luteolin, a recently discovered fructokinase inhibitor. This study demonstrates a role for fructokinase and endogenous fructose as mediators of acute renal disease.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14181

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DOI: 10.1038/ncomms14181

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