Aberrant NAD synthetic flux in podocytes under diabetic conditions and effects of indoleamine 2,3-dioxygenase on promoting de novo NAD synthesis

• DOI: 10.1016/j.bbrc.2022.12.059
• Publication Date: 2022-12-21T07:01:40Z
• Authors: Yuhua Zhang; Xingchen Zhao; Cuili Li; Yan Yang; Luan Li; Yingwen Chen; Qingying Shi; Zhilian Li; Yanhua Wu; Li Zhang; Ruizhao Li; Meijun Si; Xinling Liang; Yuanhan Chen
• Keywords: Indoleamine 2,3-dioxygenase

Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme in the kidney. The first step de novo NAD synthesis regulated by indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme. Here, we investigated synthetic flux and levels podocytes under diabetic conditions. We also studied effects of IDO overexpression on high glucose (HG)-induced podocyte injury. synthetases novo, Preiss-Handler salvage pathways were analyzed using vivo single-nucleus RNA sequencing datasets (GSE131882) control kidney disease (DKD). mRNA these measured vitro HG-treated podocytes. examined transducing cultured with adenovirus encoding IDO, apoptosis, markers mobility investigated. Cellular transcriptome analysis revealed that had relatively low synthetases. In DKD podocytes, synthetase further downregulated. virtually undetectable did not increase DKD. experiments confirmed aberrant decreased Overexpression promoted synthesis, reduced NAD-bypass metabolic enzyme, increased content recovered injury Taken together, our findings suggest DKD, promotes levels, as well alleviates