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Tytuł:
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CEES-induced ROS accumulation regulates mitochondrial complications and inflammatory response in keratinocytes.
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Autorzy:
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Sabnam S; School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India.
Rizwan H; School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India.
Pal S; School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India.
Pal A; School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India; Department of Zoology, School of Life Sciences, Mahatma Gandhi Central University, Motihari, Bihar, 845401, India. Electronic address: .
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Źródło:
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Chemico-biological interactions [Chem Biol Interact] 2020 Apr 25; Vol. 321, pp. 109031. Date of Electronic Publication: 2020 Mar 03.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Limerick : Elsevier
Original Publication: Amsterdam, Elsevier.
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MeSH Terms:
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Keratinocytes/*drug effects
Keratinocytes/*metabolism
Mustard Gas/*analogs & derivatives
Reactive Oxygen Species/*metabolism
Animals ; Cell Line ; Chemical Warfare Agents/toxicity ; DNA Damage ; DNA, Mitochondrial/metabolism ; Humans ; Inflammation/chemically induced ; Inflammation/metabolism ; Inflammation/pathology ; Irritants/toxicity ; Keratinocytes/pathology ; Membrane Potential, Mitochondrial/drug effects ; Mice ; Mice, Hairless ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondria/pathology ; Mustard Gas/toxicity ; Oxidative Stress/drug effects ; Signal Transduction/drug effects
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Contributed Indexing:
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Keywords: CEES; IRF3; Inflammation; Keratinocytes; Mitochondrial dysfunction; ROS
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Substance Nomenclature:
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0 (Chemical Warfare Agents)
0 (DNA, Mitochondrial)
0 (Irritants)
0 (Reactive Oxygen Species)
693-07-2 (2-chloroethyl ethyl sulfide)
T8KEC9FH9P (Mustard Gas)
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Entry Date(s):
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Date Created: 20200307 Date Completed: 20200330 Latest Revision: 20200330
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Update Code:
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20240105
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DOI:
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10.1016/j.cbi.2020.109031
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PMID:
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32142722
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Reactive oxygen species (ROS) is mainly produced as a by-product from electron transport chain (ETC) of mitochondria and effectively eliminated by cellular antioxidants. However, 2-chloroethyl ethyl sulfide (CEES) exposure to keratinocytes declined antioxidant capacity and increased accumulation of ROS triggered alteration of mitochondrial activity and apoptosis is lacking. Our findings demonstrated that the electron leakage from the impaired ETC, leading to the accumulation of ROS was gradually elevating with increasing concentration of CEES exposure, which decline the activity of superoxide dismutase (SOD), manganese SOD (MnSOD) and copper-zinc SOD (Cu-ZnSOD) in keratinocytes. Further, excess accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial mass with increasing dose of CEES. CEES exposure provoked the decrease in expression of transcription factor A mitochondrial (TFAM), augmented mitochondrial DNA (mtDNA) damage and altered the mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Moreover, fragmented mtDNA translocated into cytosol, where it activated cGAS-STING and interferon regulatory factor3 (IRF3), coinciding with the increased expression of inflammatory mediators and alteration of cell-to-cell communication markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or L-Nω-nitroarginine methyl ester (NAME), hydralazine hydrochloride (Hyd·HCl) or ERK1/2 or phosphoinositide3-kinase (PI3-K)/Akt inhibitors in keratinocyte cells significantly restored the CEES effect. Our findings suggest that CEES-induced mitochondrial ROS production and accumulation leads to mitochondrial dysfunction and inflammatory response in keratinocytes. However, treatment of antioxidants or ERK1/2 or PI3-K/Akt inhibitors is a novel therapeutic option for the keratinocytes complication.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier B.V. All rights reserved.)