ArticleThe American journal of pathology2000
Changes in free and esterified cholesterol: hallmarks of acute renal tubular injury and acquired cytoresistance.
Article in The American journal of pathology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- The dysregulation of metabolic pathways and induction of the pentose phosphate pathway in renal ischaemia-reperfusion injury.The Journal of pathology · 2021Article
- Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu.Scientific reports · 2021Article
- Oxidative Stress and Lymphocyte Alterations in Chronic Relapsing Experimental Allergic Encephalomyelitis in the Rat Hippocampus and Protective Effects of an Ethanolamine Phosphate Salt.Molecular neurobiology · 2020Article
- Cellular and Molecular Mechanisms of AKI.Journal of the American Society of Nephrology : JASN · 2016Review
- Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End Products.BioMed research international · 2016Article
- The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury.PloS one · 2015Article
- 'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2013Review
- Cholesterol Contributes to Diabetic Nephropathy through SCAP-SREBP-2 Pathway.International journal of endocrinology · 2013Article
- HMG-CoA reductase activation and urinary pellet cholesterol elevations in acute kidney injury.Clinical journal of the American Society of Nephrology : CJASN · 2011Article
- Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning.American journal of physiology. Regulatory, integrative and comparative physiology · 2010Article
- Steroidogenic acute regulatory-related lipid transfer domain protein 5 localization and regulation in renal tubules.American journal of physiology. Renal physiology · 2009Article
- Uremia induces proximal tubular cytoresistance and heme oxygenase-1 expression in the absence of acute kidney injury.American journal of physiology. Renal physiology · 2009Article
- Renal ischemia-induced cholesterol loading: transcription factor recruitment and chromatin remodeling along the HMG CoA reductase gene.The American journal of pathology · 2009Article
- The nephrotoxicity risk in rats subjected to heavy muscle activity.Journal of sports science & medicine · 2009Article
- Growth and development alter susceptibility to acute renal injury.Kidney international · 2008Article
- Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Acute tubular injury causes dysregulation of cellular cholesterol transport proteins.The American journal of pathology · 2003Article
- Experimental glomerulopathy alters renal cortical cholesterol, SR-B1, ABCA1, and HMG CoA reductase expression.The American journal of pathology · 2003Article
- The mevalonate pathway during acute tubular injury: selected determinants and consequences.The American journal of pathology · 2002Article
- Renal cholesterol accumulation: a durable response after acute and subacute renal insults.The American journal of pathology · 2001Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Acute tubular cell injury is accompanied by plasma membrane phospholipid breakdown. Although cholesterol is a dominant membrane lipid which interdigitates with, and impacts, phospholipid homeostasis, its fate during the induction and recovery phases of acute renal failure (ARF) has remained ill defined. The present study was performed to ascertain whether altered cholesterol expression is a hallmark of evolving tubular damage. Using gas chromatographic analysis, free cholesterol (FC) and esterified cholesterol (CE) were quantified in: 1) isolated mouse proximal tubule segments (PTS) after 30 minutes of hypoxic or oxidant (ferrous ammonium sulfate) injury; 2) cultured proximal tubule (HK-2) cells after 4 or 18 hours of either ATP depletion/Ca(2+) ionophore- or ferrous ammonium sulfate-mediated injury; and 3) in renal cortex 18 hours after induction of glycerol-induced myoglobinuric ARF, a time corresponding to the so-called "acquired cytoresistance" state (ie, resistance to further renal damage). Hypoxic and oxidant injury each induced approximately 33% decrements in CE (but not FC) levels in PTS, corresponding with lethal cell injury ( approximately 50 to 60% LDH release). When comparable CE declines were induced in normal PTS by exogenous cholesterol esterase treatment, proportionate lethal cell injury resulted. During models of slowly evolving HK-2 cell injury, progressive CE increments occurred: these were first noted at 4 hours, and reached approximately 600% by 18 hours. In vivo myoglobinuric ARF produced comparable renal cortical CE (and to a lesser extent FC) increments. Renal CE accumulation strikingly correlated with the severity of ARF (eg, blood urea nitrogen versus CE; r, 0.84). Mevastatin blocked cholesterol accumulation in injured HK-2 cells, indicating de novo synthesis was responsible. Acute tubule injury first lowers, then raises, tubule cholesterol content. Based on previous observations that cholesterol has cytoprotectant properties, the present findings have potential relevance for both the induction and maintenance phases of ARF.
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