Efficacy of 5-aminolevulinic acid-based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway.
Apoptosis
/ drug effects
Autophagy
/ drug effects
Fibroblasts
/ drug effects
Humans
Keloid
/ metabolism
Levulinic Acids
/ pharmacology
Light
Oxidative Stress
/ drug effects
Photochemotherapy
/ methods
Photosensitizing Agents
/ pharmacology
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ drug effects
Sirtuin 1
/ metabolism
Sirtuin 3
/ metabolism
Superoxide Dismutase
/ metabolism
Aminolevulinic Acid
5-aminolevulinic acid
Autophagy
Keloid
SIRT1
SIRT3
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
03
09
2018
revised:
09
10
2018
accepted:
15
10
2018
pubmed:
28
10
2018
medline:
2
4
2019
entrez:
28
10
2018
Statut:
ppublish
Résumé
Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)-based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid-derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death.
Identifiants
pubmed: 30368039
pii: S2213-2317(18)30814-0
doi: 10.1016/j.redox.2018.10.011
pmc: PMC6205077
pii:
doi:
Substances chimiques
Levulinic Acids
0
Photosensitizing Agents
0
Reactive Oxygen Species
0
Superoxide Dismutase
EC 1.15.1.1
superoxide dismutase 2
EC 1.15.1.1
Sirtuin 1
EC 3.5.1.-
Sirtuin 3
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
195-203Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Références
Medicina (Kaunas). 2003;39(7):677-82
pubmed: 12878823
Br J Dermatol. 2016 Sep;175(3):512-9
pubmed: 26931503
Neurochem Int. 2010 Oct;57(3):198-205
pubmed: 20546814
Cell Metab. 2017 Oct 3;26(4):633-647.e7
pubmed: 28978427
Am J Transl Res. 2018 Feb 15;10(2):334-351
pubmed: 29511429
Photodermatol Photoimmunol Photomed. 2011 Dec;27(6):334-5
pubmed: 22092740
J Invest Dermatol. 2017 May;137(5):1051-1059
pubmed: 28108300
Plast Reconstr Surg. 2015 Oct;136(4):715-27
pubmed: 26090767
J Invest Dermatol. 2003 Feb;120(2):325-31
pubmed: 12542540
Autophagy. 2013 Nov 1;9(11):1780-800
pubmed: 24121705
Eur J Pharmacol. 2010 Oct 25;645(1-3):14-22
pubmed: 20655907
Br J Dermatol. 2004 Oct;151(4):776-83
pubmed: 15491416
Autophagy. 2016;12(1):1-222
pubmed: 26799652
Antioxid Redox Signal. 2014 Apr 1;20(10):1646-54
pubmed: 23886445
Photochem Photobiol. 2006 Sep-Oct;82(5):1198-210
pubmed: 16808593
Cell Death Differ. 2015 Mar;22(3):367-76
pubmed: 25257169
Oxid Med Cell Longev. 2010 May-Jun;3(3):168-77
pubmed: 20716941
Biochem J. 2013 Sep 1;454(2):249-57
pubmed: 23767918
Cell Death Differ. 2008 Oct;15(10):1572-81
pubmed: 18551130
Cell Metab. 2010 Dec 1;12(6):662-7
pubmed: 21109198
PLoS One. 2012;7(12):e51974
pubmed: 23251668
Artif Cells Nanomed Biotechnol. 2018 Jan 9;:1-9
pubmed: 29313384
Autophagy. 2013 Feb 1;9(2):196-207
pubmed: 23182854
Arch Dermatol Res. 2014 May;306(4):347-57
pubmed: 24402284
ACS Appl Mater Interfaces. 2018 May 9;10(18):15494-15503
pubmed: 29682957
Apoptosis. 2016 Jun;21(6):749-60
pubmed: 27108344
Clin Cancer Res. 2016 May 15;22(10):2496-507
pubmed: 26655844
Mol Cell. 2012 Oct 26;48(2):158-67
pubmed: 23102266
J Cell Physiol. 2015 Sep;230(9):2098-107
pubmed: 25640014
Autophagy. 2014 Feb;10(2):296-310
pubmed: 24389959
Cell Death Differ. 2018 Nov;25(11):1921-1937
pubmed: 30042494
Exp Gerontol. 2013 Jul;48(7):634-9
pubmed: 22964489
J Dermatolog Treat. 2014 Oct;25(5):428-33
pubmed: 22630039
Neuron. 2014 Feb 5;81(3):471-83
pubmed: 24507186
Autophagy. 2015;11(7):1037-51
pubmed: 26120888
Int J Biol Macromol. 2018 Oct 1;117:225-234
pubmed: 29803744
Photodiagnosis Photodyn Ther. 2017 Sep;19:140-152
pubmed: 28647616
J Cell Physiol. 2018 Oct;233(10):6839-6850
pubmed: 29691838
Mol Cell. 2010 Dec 22;40(6):893-904
pubmed: 21172655
Autophagy. 2018;14(7):1239-1255
pubmed: 29912629