Nonesterified free fatty acids enhance the inflammatory response in renal tubules by inducing extracellular ATP release

American Journal of Physiology. Renal Physiology
Hong SunXiong Z Ruan

Abstract

In proteinuric renal diseases, excessive plasma nonesterified free fatty acids bound to albumin can leak across damaged glomeruli to be reabsorbed by renal proximal tubular cells and cause inflammatory tubular cells damage by as yet unknown mechanisms. The present study was designed to investigate these mechanisms induced by palmitic acid (PA; one of the nonesterified free fatty acids) overload. Our results show that excess PA stimulates ATP release through the pannexin 1 channel in human renal tubule epithelial cells (HK-2), increasing extracellular ATP concentration approximately threefold compared with control. The ATP release is dependent on caspase-3/7 activation induced by mitochondrial reactive oxygen species. Furthermore, extracellular ATP aggravates PA-induced monocyte chemoattractant protein-1 secretion and monocyte infiltration of tubular cells, enlarging the inflammatory response in both macrophages and HK-2 cells via the purinergic P2X7 receptor-mammalian target of rapamycin-forkhead box O1-thioredoxin-interacting protein/NOD-like receptor protein 3 inflammasome pathway. Hence, PA increases mitochondrial reactive oxygen species-induced ATP release and inflammatory stress, which cause a "first hit," while ATP itself...Continue Reading

References

Mar 16, 2001·American Journal of Physiology. Renal Physiology·E I Christensen, H Birn
Mar 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Davide FerrariFrancesco Di Virgilio
May 17, 2008·Free Radical Biology & Medicine·Peter Schönfeld, Lech Wojtczak
Sep 12, 2009·Drug Metabolism and Pharmacokinetics·Ger J van der Vusse
Dec 22, 2009·Nature Immunology·Rongbin ZhouJürg Tschopp
Jan 1, 2009·Advances in Experimental Medicine and Biology·Kenneth MaieseYan Chen Shang
May 27, 2010·Nephron. Clinical Practice·Bernardo Rodríguez-Iturbe, Guillermo García García
Oct 13, 2010·Biochemical and Biophysical Research Communications·Mariko SoumuraTakashi Uzu
Oct 21, 2010·American Journal of Physiology. Endocrinology and Metabolism·Mohan R Dasu, Ishwarlal Jialal
Jun 15, 2011·Free Radical Biology & Medicine·Tetsuro KoyamaTakashi Uzu
Jul 14, 2011·Islets·Maria Fernanda Rodrigues GracianoAngelo R Carpinelli
Dec 6, 2011·Transplantation Reviews·Jose Luis Gorriz, Alberto Martinez-Castelao
Jul 14, 2012·American Journal of Physiology. Renal Physiology·Richard J BainesNigel J Brunskill
Sep 14, 2012·American Journal of Physiology. Cell Physiology·Feng XiaoGordan Kilic
Dec 25, 2012·Cardiovascular Research·Prasanth PuthanveetilBrian Rodrigues
Nov 1, 2013·Critical Care : the Official Journal of the Critical Care Forum·Philippa SleemanGavin J Murphy
Mar 8, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Daniela ImpellizzeriSalvatore Cuzzocrea
Apr 12, 2014·European Journal of Clinical Investigation·Tora AlmquistPaul Hjemdahl
Sep 10, 2014·Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences·Liyao FuFanggen Lu
Dec 4, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Xiaoxia ShiGuowen Liu
Dec 4, 2014·Current Opinion in Nephrology and Hypertension·Anne-Emilie Declèves, Kumar Sharma
May 27, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Gerhard Dahl
Dec 24, 2017·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Lei DouXiao-Ping Chen
Mar 31, 2019·Nutrients·Zhibo GaiZhenguo Wang

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Citations

May 22, 2021·Purinergic Signalling·Magdiel SalgadoJuan C Sáez
Aug 28, 2021·World Journal of Clinical Cases·Cheng-Lei ZhangYi Yang
Oct 5, 2021·Journal of Agricultural and Food Chemistry·Hong SunJianzhong Li

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Methods Mentioned

BETA
glycosylation
Assay
ELISA
PCR
electrophoresis

Software Mentioned

CellEvent
Carl
Zeiss Aim
LabWorks

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