ArticleAmerican journal of physiology. Renal physiology2015
TIGAR regulates glycolysis in ischemic kidney proximal tubules.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- TIGAR regulates intestinal mucus barrier integrity by inhibiting lactylation of G6PD/6PGD in ulcerative colitis.Nature communications · 2026Article
- Integrated single-cell and clinical transcriptomic analysis identifies blunted glycolytic activation as a hallmark of maladaptive repair in renal ischemia-reperfusion.Renal failure · 2025Article
- TIGAR coordinates senescence-associated secretory phenotype via lysosome repositioning and α-tubulin deacetylation.Experimental & molecular medicine · 2024Article
- Article
- AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated glycolysis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Cell death induced by acute renal injury: a perspective on the contributions of accidental and programmed cell death.American journal of physiology. Renal physiology · 2024Review
- Ischemia-Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2024Review
- The role of p53 in male infertility.Frontiers in endocrinology · 2024Review
- Article
- Energy metabolic reprogramming regulates programmed cell death of renal tubular epithelial cells and might serve as a new therapeutic target for acute kidney injury.Frontiers in cell and developmental biology · 2023Review
- Article
- Immunometabolic rewiring of tubular epithelial cells in kidney disease.Nature reviews. Nephrology · 2022Review
- TIGAR deficiency sensitizes angiotensin-II-induced renal fibrosis and glomerular injury.Physiological reports · 2022Article
- Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function.Metabolites · 2022Article
- Insights from the p53 induced TIGAR protein 2 in the glycolytic pathway model.Bioinformation · 2022Article
- Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- The dual role of the hexosamine biosynthetic pathway in cardiac physiology and pathophysiology.Frontiers in endocrinology · 2022Review
- The role of TIGAR in nervous system diseases.Frontiers in aging neuroscience · 2022Review
- Review
- The dysregulation of metabolic pathways and induction of the pentose phosphate pathway in renal ischaemia-reperfusion injury.The Journal of pathology · 2021Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Tp53-induced glycolysis and apoptosis regulator (TIGAR) activation blocks glycolytic ATP synthesis by inhibiting phosphofructokinase-1 activity. Our data indicate that TIGAR is selectively induced and activated in renal outermedullary proximal straight tubules (PSTs) after ischemia-reperfusion injury in a p53-dependent manner. Under severe ischemic conditions, TIGAR expression persisted through 48 h postinjury and induced loss of renal function and histological damage. Furthermore, TIGAR upregulation inhibited phosphofructokinase-1 activity, glucose 6-phosphate dehydrogenase (G6PD) activity, and induced ATP depletion, oxidative stress, autophagy, and apoptosis. Small interfering RNA-mediated TIGAR inhibition prevented the aforementioned malevolent effects and protected the kidneys from functional and histological damage. After mild ischemia, but not severe ischemia, G6PD activity and NADPH levels were restored, suggesting that TIGAR activation may redirect the glycolytic pathway into gluconeogenesis or the pentose phosphate pathway to produce NADPH. The increased level of NADPH maintained the level of GSH to scavenge ROS, resulting in a lower sensitivity of PST cells to injury. Under severe ischemia, G6PD activity and NADPH levels were reduced during reperfusion; however, blockade of TIGAR enhanced their levels and reduced oxidative stress and apoptosis. Collectively, these results demonstrate that inhibition of TIGAR may protect PST cells from energy depletion and apoptotic cell death in the setting of severe ischemia-reperfusion injury. However, under low ischemic burden, TIGAR activation induces the pentose phosphate pathway and autophagy as a protective mechanism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.