NAD+激酶
肾病
肾脏疾病
肾
医学
疾病
人类免疫缺陷病毒(HIV)
病理
病毒学
免疫学
内分泌学
生物
糖尿病
生物化学
酶
作者
Teruhiko Yoshida,Komuraiah Myakala,Bryce A. Jones,Xiaoxin X. Wang,Shashi Shrivastav,Briana A. Santo,Tatsat R. Patel,Yongmei Zhao,Vincent M. Tutino,Pinaki Sarder,Avi Z. Rosenberg,Cheryl A. Winkler,Moshe Levi,Jeffrey B. Kopp
出处
期刊:American Journal of Physiology-renal Physiology
[American Physiological Society]
日期:2024-07-04
标识
DOI:10.1152/ajprenal.00061.2024
摘要
HIV disease remains prevalent in the USA and is particularly prevalent in sub-Saharan Africa. Recent investigations revealed that mitochondrial dysfunction in kidney contributes to HIV-associated nephropathy (HIVAN) in Tg26 transgenic mice. We hypothesized that nicotinamide adenine dinucleotide (NAD) deficiency contributes to energetic dysfunction and progressive tubular injury. We investigated metabolomic mechanisms of HIVAN tubulopathy. Tg26 and wild-type (WT) mice were treated with the farnesoid-X receptor (FXR) agonist INT-747 or nicotinamide riboside (NR) from 6 to 12 weeks of age. Multi-omic approaches were used to characterize kidney tissue transcriptomes and metabolomes. Treatment with INT-747 or NR ameliorated kidney tubular injury, as shown by serum creatinine, the tubular injury marker urinary neutrophil-associated lipocalin and tubular morphometry. Integrated analysis of metabolomic and transcriptomic measurements showed that NAD levels and production were globally downregulated in Tg26 mouse kidney, especially nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway. Further, NAD-dependent deacetylase sirtuin3 activity and mitochondrial oxidative phosphorylation activity were lower in
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