A new role of glutathione peroxidase 4 during human erythroblast enucleation.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
24 11 2020
24 11 2020
Historique:
received:
03
08
2020
accepted:
13
10
2020
entrez:
19
11
2020
pubmed:
20
11
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
The selenoprotein glutathione peroxidase 4 (GPX4), the only member of the glutathione peroxidase family able to directly reduce cell membrane-oxidized fatty acids and cholesterol, was recently identified as the central regulator of ferroptosis. GPX4 knockdown in mouse hematopoietic cells leads to hemolytic anemia and to increased spleen erythroid progenitor death. The role of GPX4 during human erythropoiesis is unknown. Using in vitro erythroid differentiation, we show here that GPX4-irreversible inhibition by 1S,3R-RSL3 (RSL3) and its short hairpin RNA-mediated knockdown strongly impaired enucleation in a ferroptosis-independent manner not restored by tocopherol or iron chelators. During enucleation, GPX4 localized with lipid rafts at the cleavage furrows between reticulocytes and pyrenocytes. Its inhibition impacted enucleation after nuclear condensation and polarization and was associated with a defect in lipid raft clustering (cholera toxin staining) and myosin-regulatory light-chain phosphorylation. Because selenoprotein translation and cholesterol synthesis share a common precursor, we investigated whether the enucleation defect could represent a compensatory mechanism favoring GPX4 synthesis at the expense of cholesterol, known to be abundant in lipid rafts. Lipidomics and filipin staining failed to show any quantitative difference in cholesterol content after RSL3 exposure. However, addition of cholesterol increased cholera toxin staining and myosin-regulatory light-chain phosphorylation, and improved enucleation despite GPX4 knockdown. In summary, we identified GPX4 as a new actor of human erythroid enucleation, independent of its function in ferroptosis control. We described its involvement in lipid raft organization required for contractile ring assembly and cytokinesis, leading in fine to nucleus extrusion.
Identifiants
pubmed: 33211827
pii: S2473-9529(20)31965-0
doi: 10.1182/bloodadvances.2020003100
pmc: PMC7686909
doi:
Substances chimiques
Phospholipid Hydroperoxide Glutathione Peroxidase
EC 1.11.1.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5666-5680Informations de copyright
© 2020 by The American Society of Hematology.
Références
Curr Opin Hematol. 2009 May;16(3):187-94
pubmed: 19318943
Blood. 2011 Nov 10;118(19):5071-9
pubmed: 21885599
Free Radic Biol Med. 2003 Feb 15;34(4):496-502
pubmed: 12566075
PLoS One. 2012;7(6):e38733
pubmed: 22723880
Methods. 2017 Jan 1;112:68-74
pubmed: 27582124
Blood. 1989 Aug 15;74(3):1112-20
pubmed: 2752157
Mol Cell Biol. 2016 Dec 19;37(1):
pubmed: 27795297
Blood. 2014 Dec 4;124(24):3636-45
pubmed: 25339359
Mol Cell Biol. 2005 Jun;25(12):5205-14
pubmed: 15923635
Database (Oxford). 2017 Jan 1;2017:
pubmed: 28605766
Blood. 2016 Sep 22;128(12):1631-41
pubmed: 27480112
Redox Biol. 2018 Apr;14:41-46
pubmed: 28865296
PLoS One. 2016 Jan 05;11(1):e0146201
pubmed: 26731108
Genes Dev. 2011 Jan 15;25(2):119-24
pubmed: 21196494
Semin Hematol. 2011 Apr;48(2):106-16
pubmed: 21435507
Blood. 2012 Jun 21;119(25):6118-27
pubmed: 22461493
J Cell Biol. 1989 Dec;109(6 Pt 1):3005-13
pubmed: 2574178
Haematologica. 2020 Mar;105(3):610-622
pubmed: 31413092
Nat Commun. 2019 Apr 8;10(1):1617
pubmed: 30962421
Blood Adv. 2019 Nov 12;3(21):3337-3350
pubmed: 31698463
Haematologica. 2020 Apr;105(4):937-950
pubmed: 31248967
J Biol Chem. 2000 Sep 15;275(37):28421-7
pubmed: 10893423
Nature. 2019 Nov;575(7784):693-698
pubmed: 31634899
Curr Opin Hematol. 2017 May;24(3):191-197
pubmed: 28072603
Mol Cell Biol. 2012 Apr;32(8):1396-407
pubmed: 22331463
J Neurosci Res. 2006 Jul;84(1):202-8
pubmed: 16673405
Biochemistry. 2002 Feb 12;41(6):1742-51
pubmed: 11827518
Nucleic Acids Res. 2016 Jan 4;44(D1):D917-24
pubmed: 26507857
Neurobiol Dis. 2016 Oct;94:169-78
pubmed: 27189756
Free Radic Biol Med. 2019 Mar;133:130-143
pubmed: 30268886
Blood. 2010 Oct 28;116(17):3331-40
pubmed: 20644112
J Am Chem Soc. 2014 Mar 26;136(12):4551-6
pubmed: 24592866
Front Pharmacol. 2018 Nov 22;9:1371
pubmed: 30524291
Blood. 2016 Jan 7;127(1):139-48
pubmed: 26463424
Blood. 2001 Feb 15;97(4):1141-3
pubmed: 11159550
Blood. 1983 Jun;61(6):1242-6
pubmed: 6188507
PLoS One. 2019 Mar 28;14(3):e0208659
pubmed: 30921348
Cell Death Discov. 2019 Feb 28;5:69
pubmed: 30854228
Cell. 2014 Jan 16;156(1-2):317-331
pubmed: 24439385
Proteomics. 2019 Sep;19(18):e1800311
pubmed: 30888116
Cell Rep. 2016 Aug 2;16(5):1470-1484
pubmed: 27452463
J Biol Chem. 2000 Sep 8;275(36):28110-9
pubmed: 10821829
Curr Opin Hematol. 2014 May;21(3):165-71
pubmed: 24492678
Nat Cell Biol. 2014 Dec;16(12):1180-91
pubmed: 25402683
Acta Pharmacol Sin. 2019 Oct;40(10):1334-1342
pubmed: 31036877
Trends Cell Biol. 2016 Mar;26(3):165-176
pubmed: 26653790
Nature. 2005 Sep 29;437(7059):754-8
pubmed: 16193055
Blood Adv. 2018 Oct 23;2(20):2787-2797
pubmed: 30352953
Haematologica. 2010 Dec;95(12):2013-21
pubmed: 20823130
Mol Psychiatry. 2017 Nov;22(11):1520-1530
pubmed: 28886009
Am J Hum Genet. 2010 Nov 12;87(5):721-7
pubmed: 21055716
Stem Cell Res Ther. 2019 Apr 29;10(1):130
pubmed: 31036072
Ann N Y Acad Sci. 2016 Mar;1368(1):149-61
pubmed: 26890363
Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):E4966-75
pubmed: 27506793
Methods Cell Biol. 2017;137:15-24
pubmed: 28065303
Blood. 1992 Aug 1;80(3):642-50
pubmed: 1638021
Methods Mol Biol. 2018;1698:175-192
pubmed: 29076090
Cell Death Dis. 2018 Jul 9;9(7):753
pubmed: 29988039
Blood. 2004 Mar 1;103(5):1912-9
pubmed: 14563645
Cell Regen. 2018 Nov 27;7(2):45-49
pubmed: 30671230
Methods Mol Biol. 2018;1698:193-203
pubmed: 29076091
Cancer Cell. 2018 May 14;33(5):890-904.e5
pubmed: 29657129
Front Pharmacol. 2019 Jun 07;10:638
pubmed: 31231224
Dev Cell. 2019 Dec 2;51(5):575-586.e4
pubmed: 31735663
Blood. 2013 Apr 18;121(16):3246-53
pubmed: 23422750
Chromosome Res. 2009;17(1):47-64
pubmed: 19172406
Front Physiol. 2019 Dec 20;10:1529
pubmed: 31920725
Free Radic Biol Med. 2018 Nov 1;127:153-159
pubmed: 29522794
J Cell Physiol. 1994 Sep;160(3):417-26
pubmed: 8077279
J Cell Biol. 1967 Jun;33(3):625-35
pubmed: 6036525
Nat Cell Biol. 2008 Mar;10(3):314-21
pubmed: 18264091
Leukemia. 2015 Jul;29(7):1452-7
pubmed: 25748684
PLoS One. 2013;8(4):e60300
pubmed: 23565219
Mol Cell Biol. 2014 Oct 1;34(19):3721-34
pubmed: 25071156
Redox Biol. 2018 Apr;14:535-548
pubmed: 29126071
Sci Rep. 2018 Aug 24;8(1):12793
pubmed: 30143664
Cell Rep. 2020 Mar 10;30(10):3411-3423.e7
pubmed: 32160546
Science. 2010 Jan 1;327(5961):46-50
pubmed: 20044567
J Biol Chem. 2020 Jun 5;295(23):8048-8063
pubmed: 32358067
Nucleic Acids Res. 2017 Feb 17;45(3):1130-1143
pubmed: 28180284
Dev Cell. 2014 Sep 29;30(6):688-700
pubmed: 25241935
Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2672-2680
pubmed: 30692261
Exp Cell Res. 1970 Jun;60(3):427-36
pubmed: 5422968
Dev Cell. 2005 Dec;9(6):781-90
pubmed: 16326390
Cytometry. 1984 Jan;5(1):42-54
pubmed: 6199166
Mol Pharmacol. 2009 Jun;75(6):1421-9
pubmed: 19332511
Hepatology. 2017 Aug;66(2):449-465
pubmed: 28195347
J Biol Chem. 2009 Oct 30;284(44):30484-97
pubmed: 19729679
Nature. 1997 Jun 5;387(6633):569-72
pubmed: 9177342
Cell. 2012 May 25;149(5):1060-72
pubmed: 22632970
Cancer Med. 2019 Mar;8(3):1169-1174
pubmed: 30701702
BMC Genomics. 2019 May 24;20(1):417
pubmed: 31126231