8-Chloroadenosine induces apoptosis in human coronary artery endothelial cells through the activation of the unfolded protein response.
2-Chloroadenosine
/ analogs & derivatives
Antioxidants
/ metabolism
Apoptosis
/ drug effects
Cell Line
Coronary Vessels
/ metabolism
DNA
/ chemistry
Endothelial Cells
/ drug effects
Glycolysis
/ drug effects
Human Umbilical Vein Endothelial Cells
Humans
Mitochondria
/ drug effects
Oxidation-Reduction
/ drug effects
RNA
/ chemistry
Unfolded Protein Response
/ drug effects
DNA
Hypochlorous acid
Inflammation
Myeloperoxidase
Nucleoside
RNA
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
10
04
2019
revised:
05
07
2019
accepted:
09
07
2019
pubmed:
16
7
2019
medline:
28
2
2020
entrez:
16
7
2019
Statut:
ppublish
Résumé
Infiltration of leukocytes within the vessel at sites of inflammation and the subsequent generation of myeloperoxidase-derived oxidants, including hypochlorous acid, are key characteristics of atherosclerosis. Hypochlorous acid is a potent oxidant that reacts readily with most biological molecules, including DNA and RNA. This results in nucleic acid modification and the formation of different chlorinated products. These products have been used as biomarkers of inflammation, owing to their presence in elevated amounts in different inflammatory fluids and diseased tissue, including atherosclerotic lesions. However, it is not clear whether these materials are simply biomarkers, or could also play a role in the development of chronic inflammatory pathologies. In this study, we examined the reactivity of different chlorinated nucleosides with human coronary artery endothelial cells (HCAEC). Evidence was obtained for the incorporation of each chlorinated nucleoside into the cellular RNA or DNA. However, only 8-chloro-adenosine (8ClA) had a significant effect on the cell viability and metabolic activity. Exposure of HCAEC to 8ClA decreased glycolysis, and resulted in a reduction in ATP, with a corresponding increase in the chlorinated analogue, 8Cl-ATP in the nucleotide pool. 8ClA also induced sustained endoplasmic reticulum stress within the HCAEC, which resulted in activation of the unfolded protein response, the altered expression of antioxidant genes and culminated in the release of calcium into the cytosol and cell death by apoptosis. Taken together, these data provide new insight into pathways by which myeloperoxidase activity and resultant hypochlorous acid generation could promote endothelial cell damage during chronic inflammation, which could be relevant to the progression of atherosclerosis.
Identifiants
pubmed: 31307008
pii: S2213-2317(19)30430-6
doi: 10.1016/j.redox.2019.101274
pmc: PMC6629973
pii:
doi:
Substances chimiques
Antioxidants
0
2-Chloroadenosine
146-77-0
RNA
63231-63-0
DNA
9007-49-2
8-chloroadenosine
PA05MFH3I7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101274Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
Références
Redox Biol. 2015 Dec;6:183-197
pubmed: 26233704
Chem Res Toxicol. 2010 Jul 19;23(7):1293-302
pubmed: 20593802
Curr Biol. 2012 Aug 21;22(16):R622-6
pubmed: 22917505
Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2045-51
pubmed: 22895665
Science. 1985 Mar 8;227(4691):1231-3
pubmed: 3975611
J Neuroinflammation. 2017 May 11;14(1):104
pubmed: 28490373
Semin Immunopathol. 2013 May;35(3):321-32
pubmed: 23553213
Biomarkers. 1999;4(4):303-10
pubmed: 23889180
J Biol Chem. 2003 Jun 27;278(26):23522-8
pubmed: 12707270
J Biol Chem. 2006 Feb 10;281(6):3096-104
pubmed: 16326702
JAMA. 2001 Nov 7;286(17):2136-42
pubmed: 11694155
Antioxid Redox Signal. 2008 Jul;10(7):1199-234
pubmed: 18331199
Br J Haematol. 2009 Nov;147(3):297-307
pubmed: 19709085
Redox Rep. 2017 Mar;22(2):51-73
pubmed: 27884085
Cancer Chemother Pharmacol. 2002 Aug;50(2):85-94
pubmed: 12172971
J Hematol Oncol. 2014 Mar 14;7:23
pubmed: 24628795
J Chromatogr. 1987 Jan 23;413:293-9
pubmed: 3558682
Cancer Res. 1980 Apr;40(4):1235-9
pubmed: 6244089
Biochem Pharmacol. 2002 Nov 15;64(10):1493-502
pubmed: 12417262
J Biol Chem. 2010 Mar 19;285(12):9282-91
pubmed: 20081197
Breast Cancer Res Treat. 2010 Jun;121(2):355-64
pubmed: 19641990
Methods Enzymol. 2011;489:109-26
pubmed: 21266227
Mol Cell Biochem. 2017 May;429(1-2):59-71
pubmed: 28074342
Chem Res Toxicol. 2001 Aug;14(8):1071-81
pubmed: 11511181
Mutat Res. 1993 Jul;297(1):39-51
pubmed: 7686272
Nat Rev Mol Cell Biol. 2012 Jan 18;13(2):89-102
pubmed: 22251901
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Nov 15;827(1):26-31
pubmed: 16260376
Free Radic Biol Med. 2014 Jun;71:240-55
pubmed: 24632382
Biochem Pharmacol. 1997 Jan 24;53(2):141-8
pubmed: 9037246
Talanta. 2016 Jul 1;154:322-8
pubmed: 27154681
Biochem Pharmacol. 2009 Sep 15;78(6):583-91
pubmed: 19477165
Anal Biochem. 2003 Jun 15;317(2):201-9
pubmed: 12758258
Clin Cancer Res. 1995 Apr;1(4):377-84
pubmed: 9815994
Diabetologia. 2018 Feb;61(2):399-412
pubmed: 28988346
J Cell Physiol. 2009 Jan;218(1):104-12
pubmed: 18756496
Circulation. 2004 Aug 31;110(9):1134-9
pubmed: 15326065
Blood. 2005 Jun 1;105(11):4455-62
pubmed: 15718423
Cancer Res. 2001 Jul 15;61(14):5474-9
pubmed: 11454694
Mutat Res. 1981 Jul-Sep;91(4-5):395-401
pubmed: 7266579
Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):E4571-80
pubmed: 26243878
Circ Res. 2010 Oct 1;107(7):839-50
pubmed: 20884885
Blood. 1990 Aug 15;76(4):655-63
pubmed: 2200535
EMBO Mol Med. 2014 May 19;6(6):732-43
pubmed: 24843047
Cancer Res. 2003 Nov 15;63(22):7968-74
pubmed: 14633728