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Cell stress response impairs de novo NAD+ biosynthesis in the kidney

Abstract : The biosynthetic routes leading to de novo Nicotinamine Adenine Dinucleotide (NAD+) production are involved in acute kidney injury (AKI) with a critical role for Quinolinate Phosphoribosyl Transferase (QPRT), a bottleneck enzyme of de novo NAD + biosynthesis. However, the molecular mechanisms determining reduced QPRT in AKI, and the role of impaired NAD + biosynthesis in the progression to chronic kidney disease (CKD) are unknown. We demonstrate that a high urinary quinolinate to tryptophan ratio, an indirect indicator of impaired QPRT activity and reduced de novo NAD + biosynthesis in the kidney, is a clinically applicable early marker of AKI after cardiopulmonary bypass, and is predictive of progression to chronic kidney disease (CKD) in kidney transplant recipients. We also provide evidence that the Endoplasmic Reticulum (ER) stress response impairs de novo NAD + biosynthesis by repressing QPRT transcription. In conclusion, NAD + biosynthesis impairment is an early event in AKI embedded with the ER stress response, and persistent reduction of QPRT expression is associated with AKI to CKD progression. This defines non-invasive metabolic biomarkers of kidney injury with prognostic and therapeutic implications.
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https://hal.sorbonne-universite.fr/hal-03442936
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Submitted on : Tuesday, November 23, 2021 - 12:15:49 PM
Last modification on : Thursday, November 25, 2021 - 11:07:24 AM

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Yohan Bignon, Anna Rinaldi, Zahia Nadour, Virginie Poindessous, Ivan Nemazanyy, et al.. Cell stress response impairs de novo NAD+ biosynthesis in the kidney. JCI Insight, American Society for Clinical Investigation, 2021, ⟨10.1172/jci.insight.153019⟩. ⟨hal-03442936⟩

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