Transcriptional regulation of proximal tubular metabolism in acute kidney injury.
The kidney, and in particular the proximal tubule (PT), has a high demand for ATP, due to its function in bulk reabsorption of solutes. In normal PT, ATP levels are predominantly maintained by fatty acid β-oxidation (FAO), the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. The normal...
| Published in: | Pediatric Nephrology Vol. 38; no. 4; pp. 975 - 987 |
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| Main Authors: | , |
| Format: | review tables/charts Journal Article |
| Published: |
Springer Nature
Apr2023
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=161854867&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 161854867 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0931041X EF1 jtl: Pediatric Nephrology issn: 0931041X maglogo: N pubinfo: dt: Apr2023 vid: 38 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 161854867 161854867 161854867 10.1007/s00467-022-05748-2 161854867 ppf: 975 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Transcriptional regulation of proximal tubular metabolism in acute kidney injury. aug: au: Piret, Sian E. Mallipattu, Sandeep K. affil: Division of Nephrology and Hypertension, Department of Medicine, Stony Brook University, 101 Nicolls Road, 11794, Stony Brook, NY, USA sug: subj: Kidney Failure, Acute Familial and Genetic Kidney Failure, Acute Metabolism Kidney Tubules Metabolism Reperfusion Injury Metabolism Metabolic Networks and Pathways Tricarboxylic Acids Phosphorylation Carbohydrate Metabolism Amino Acids Metabolism Genes Kidney Metabolism Adenosine Triphosphatase Metabolism Fatty Acids Metabolism ab: The kidney, and in particular the proximal tubule (PT), has a high demand for ATP, due to its function in bulk reabsorption of solutes. In normal PT, ATP levels are predominantly maintained by fatty acid β-oxidation (FAO), the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. The normal PT also undertakes gluconeogenesis and metabolism of amino acids. Acute kidney injury (AKI) results in profound PT metabolic alterations, including suppression of FAO, gluconeogenesis, and metabolism of some amino acids, and upregulation of glycolytic enzymes. Recent studies have elucidated new transcriptional mechanisms regulating metabolic pathways in normal PT, as well as the metabolic switch in AKI. A number of transcription factors have been shown to play important roles in FAO, which are themselves downregulated in AKI, while hypoxia-inducible factor 1α, which is upregulated in ischemia–reperfusion injury, is a likely driver of the upregulation of glycolytic enzymes. Transcriptional regulation of amino acid metabolic pathways is less well understood, except for catabolism of branched-chain amino acids, which is likely suppressed in AKI by upregulation of Krüppel-like factor 6. This review will focus on the transcriptional regulation of specific metabolic pathways in normal PT and in AKI, as well as highlighting some of the gaps in knowledge and challenges that remain to be addressed. pubtype: Academic Journal doctype: review tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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