Quercetin alleviates acute kidney injury by inhibiting ferroptosis.
Activation transcription factor 3
Acute kidney injury
Ferroptosis
Macrophages
Quercetin
Journal
Journal of advanced research
ISSN: 2090-1232
Titre abrégé: J Adv Res
Pays: Egypt
ID NLM: 101546952
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
26
03
2020
revised:
18
06
2020
accepted:
16
07
2020
entrez:
28
12
2020
pubmed:
29
12
2020
medline:
29
12
2020
Statut:
epublish
Résumé
Ferroptosis is an iron-dependent regulated necrosis and has been proven to contribute to the progress of acute kidney injury (AKI). Quercetin (QCT), a natural flavonoid which is commonly found in numerous fruits and vegetables, has extensive pharmacological effects, such as anti-oxidant, anti-inflammatory and anti-senescence effects. This study aims to explain whether ferroptosis is a therapeutic strategy to AKI, and to explore the effect of QCT on AKI ferroptosis. NRK-52E cells and HK-2 cells were used for in vitro ferroptosis studies. Morphology of cells was detected by transmission electron microscopy. Lipid ROS was assayed using flow cytometry. In vivo, AKI was induced by ischemia-reperfusion (I/R) or folic acid (FA). To explore the molecular mechanisms, RNA-sequence analysis was performed. Transwell was used to detect macrophage migration. We discovered that quercetin (QCT), a natural flavonoid, inhibited ferroptosis in renal proximal tubular epithelial cells. QCT blocked the typical morphologic changes of ferroptotic cells by reducing the levels of malondialdehyde (MDA) and lipid ROS and increasing the levels of glutathione (GSH). Moreover, QCT ameliorated AKI induced by I/R or FA. RNA-sequence analysis highlighted activation transcription factor 3 (ATF3), as it was the dominant one among all the 299 down-regulated genes by QCT. Knockdown of ATF3 could significantly increase the levels of SLC7A11, GPX4 and increased the cell viability. In addition, ferroptotic cells were found to be extremely pro-inflammatory by recruiting macrophages through CCL2, while QCT inhibited the chemotaxis of macrophages induced by ferroptosis in AKI. Collectively, these results identify QCT as a ferroptosis inhibitor and provide new therapeutic strategies for diseases related to ferroptosis.
Identifiants
pubmed: 33364059
doi: 10.1016/j.jare.2020.07.007
pii: S2090-1232(20)30166-1
pmc: PMC7753233
doi:
Types de publication
Journal Article
Langues
eng
Pagination
231-243Informations de copyright
© 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.
Déclaration de conflit d'intérêts
The authors have declared no conflict of interest.
Références
Nat Chem Biol. 2017 Jan;13(1):91-98
pubmed: 27842070
Nature. 2019 Nov;575(7784):693-698
pubmed: 31634899
Ren Fail. 2017 Nov;39(1):193-202
pubmed: 27845599
Crit Care Med. 2011 Nov;39(11):2487-94
pubmed: 21705900
Free Radic Res. 2002 Nov;36(11):1229-41
pubmed: 12592675
J Am Soc Nephrol. 2017 Jan;28(1):218-229
pubmed: 27352622
Am J Physiol Renal Physiol. 2018 May 1;314(5):F702-F714
pubmed: 28515173
Trends Cell Biol. 2005 Apr;15(4):179-83
pubmed: 15817372
Acta Biomater. 2018 Jul 15;75:287-299
pubmed: 29883808
J Am Soc Nephrol. 2017 Dec;28(12):3590-3604
pubmed: 28801314
Oncogene. 2017 Oct 5;36(40):5593-5608
pubmed: 28553953
Front Physiol. 2015 Sep 02;6:247
pubmed: 26388784
Am J Physiol Renal Physiol. 2006 Jan;290(1):F35-42
pubmed: 16106037
Oncogene. 2008 Apr 3;27(15):2118-27
pubmed: 17952119
Int J Cardiol. 2014 Jul 1;174(3):838-9
pubmed: 24794959
Phytother Res. 2018 Nov;32(11):2109-2130
pubmed: 30039547
Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16836-41
pubmed: 25385600
J Am Soc Nephrol. 2014 Dec;25(12):2689-701
pubmed: 24925726
Arch Toxicol. 2017 Apr;91(4):1925-1939
pubmed: 27585667
J Clin Invest. 2009 Aug;119(8):2330-42
pubmed: 19587445
Mol Cancer Ther. 2005 May;4(5):693-703
pubmed: 15897233
PLoS One. 2014 Jul 24;9(7):e102900
pubmed: 25058155
J Am Chem Soc. 2014 Mar 26;136(12):4551-6
pubmed: 24592866
Antioxidants (Basel). 2020 Mar 02;9(3):
pubmed: 32131401
Cell Adh Migr. 2019 Dec;13(1):1-12
pubmed: 29945484
Cell. 2014 Jan 16;156(1-2):317-331
pubmed: 24439385
Aging Cell. 2015 Aug;14(4):644-58
pubmed: 25754370
Nat Med. 2018 Aug;24(8):1246-1256
pubmed: 29988130
Nat Med. 2011 Dec 18;18(1):128-34
pubmed: 22179317
Nat Cell Biol. 2016 May;18(5):572-8
pubmed: 27088857
Biometals. 2000 Mar;13(1):77-83
pubmed: 10831228
Nat Cell Biol. 2014 Dec;16(12):1180-91
pubmed: 25402683
Cell Death Differ. 2020 Feb;27(2):662-675
pubmed: 31273299
Curr Gene Ther. 2019;19(4):211-215
pubmed: 31553295
Acta Pharmacol Sin. 2019 Oct;40(10):1334-1342
pubmed: 31036877
Nefrologia. 2018 Mar - Apr;38(2):125-135
pubmed: 28647049
J Hepatol. 2007 Aug;47(2):253-61
pubmed: 17433488
J Clin Invest. 2009 May;119(5):1275-85
pubmed: 19349686
Cell Death Differ. 2016 Mar;23(3):369-79
pubmed: 26794443
J Am Soc Nephrol. 2018 Mar;29(3):919-935
pubmed: 29295871
Eur J Med Chem. 2018 Jul 15;155:889-904
pubmed: 29966915
Oncotarget. 2015 Sep 15;6(27):24393-403
pubmed: 26405158
Naunyn Schmiedebergs Arch Pharmacol. 2014 Sep;387(9):823-35
pubmed: 24899384
J Exp Med. 2012 Apr 9;209(4):807-17
pubmed: 22473958
Curr Biol. 2018 Aug 6;28(15):2388-2399.e5
pubmed: 30057310
J Ethnopharmacol. 2017 Jul 12;206:152-159
pubmed: 28408246
Nat Protoc. 2006;1(3):1112-6
pubmed: 17406391
Acta Pharm Sin B. 2015 Jan;5(1):47-54
pubmed: 26579424
Nature. 2007 Jun 14;447(7146):864-8
pubmed: 17568748
Pharm Res. 2005 Jun;22(6):892-901
pubmed: 15948033
Mol Nutr Food Res. 2016 Jan;60(1):203-11
pubmed: 26310602
Cell. 2012 May 25;149(5):1060-72
pubmed: 22632970