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The Authors
Original Article
Proteome-wide changes in primary skin keratinocytes exposed to diesel particulate extract—A role for antioxidants in skin health
Pavithra
Rajagopalan
a
1
pavithra@ibioinformatics.org
Ankit P.
Jain
a
1
ankit@ibioinformatics.org
Vishalakshi
Nanjappa
a
vishalakshi@ibioinformatics.org
Krishna
Patel
a
krishnapatel@ibioinformatics.org
Kiran K.
Mangalaparthi
a
kiran@ibioinformatics.org
Niraj
Babu
a
b
niraj@ibioinformatics.org
Nükhet
Cavusoglu
c
ncavusoglu@rd.loreal.com
Nita
Roy
d
NITAROY@rd.loreal.com
Jeremie
Soeur
c
JSOEUR@rd.loreal.com
Lionel
Breton
c
LBRETON@rd.loreal.com
Akhilesh
Pandey
e
f
g
h
pandey@jhmi.edu
Harsha
Gowda
a
⁎
harsha@ibioinformatics.org
Aditi
Chatterjee
a
⁎
aditi@ibioinformatics.org
Namita
Misra
c
d
⁎⁎
NMISRA@rd.loreal.com
a
Institute of Bioinformatics, International Tech Park, Bangalore 560066, India
Institute of Bioinformatics
International Tech Park
Bangalore
560066
India
b
Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India
Manipal Academy of Higher Education (MAHE)
Manipal
Karnataka
576104
India
c
L'Oréal Research and Innovation, Aulnay sous bois, 93600, France
L'Oréal Research and Innovation
Aulnay sous bois
93600
France
d
L'Oréal India Pvt. Ltd., Beary’s Global Research Triangle, Bangalore 560067, India
L'Oréal India Pvt. Ltd.
Beary’s Global Research Triangle
Bangalore
560067
India
e
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
McKusick-Nathans Institute of Genetic Medicine
Johns Hopkins University School of Medicine
Baltimore
MD
21205
USA
f
Departments of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
Departments of Biological Chemistry
Johns Hopkins University School of Medicine
Baltimore
MD
21205
USA
g
Departments of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
Departments of Oncology
Johns Hopkins University School of Medicine
Baltimore
MD
21205
USA
h
Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Departments of Pathology
Johns Hopkins University School of Medicine
Baltimore
MD
21205
USA
⁎
Corresponding authors at: Faculty Scientist Institute of Bioinformatics 7th floor, Discoverer building, International Tech Park, Bangalore 560 066, India. Tel.:+91 80 28416140; Tel.:+91 80 28416140.
Faculty Scientist Institute of Bioinformatics 7th floor, Discoverer building, International Tech Park
Bangalore
560 066
India
⁎⁎
Corresponding author at: Department of Advanced Research, L’Oréal Research & Innovation, Aulnay sous bois 93600, France. Tel: +33 148689600.
Department of Advanced Research
L’Oréal Research & Innovation
Aulnay sous bois
93600
France
1
Equal contribution.
Highlights
•
Chronic exposure to diesel particulate extract/ its vapor cause global proteomic alterations in primary skin keratinocytes.
•
DPE/DPE vapor alter proteins involved in maintaining skin integrity in primary skin keratinocytes.
•
DPE vapor affects proteins associated with OXPHOS and cell migration in skin keratinocytes.
•
Similar effects are observed upon DPE/DPE vapor treatment in 2D and 3D skin model.
•
Vitamin E partially restores altered proteins in DPE/vapor exposed skin keratinocytes.
Abstract
Background
Skin acts as a protective barrier against direct contact with pollutants but inhalation and systemic exposure have indirect effect on keratinocytes. Exposure to diesel exhaust has been linked to increased oxidative stress.
Objective
To investigate global proteomic alterations in diesel particulate extract (DPE)/its vapor exposed skin keratinocytes.
Methods
We employed Tandem Mass Tag (TMT)-based proteomics to study effect of DPE/DPE vapor on primary skin keratinocytes.
Results
We observed an increased expression of oxidative stress response protein NRF2, upon chronic exposure of primary keratinocytes to DPE/its vapor which includes volatile components such as polycyclic aromatic hydrocarbons (PAHs). Mass spectrometry-based quantitative proteomics led to identification 4490 proteins of which 201 and 374 proteins were significantly dysregulated (≥1.5 fold, p≤0.05) in each condition, respectively. Proteins involved in cellular processes such as cornification (cornifin A), wound healing (antileukoproteinase) and differentiation (suprabasin) were significantly downregulated in primary keratinocytes exposed to DPE/DPE vapor. These results were corroborated in 3D skin models chronically exposed to DPE/DPE vapor. Bioinformatics analyses indicate that DPE and its vapor affect distinct molecular processes in skin keratinocytes. Components of mitochondrial oxidative phosphorylation machinery were seen to be exclusively overexpressed upon chronic DPE vapor exposure. In addition, treatment with an antioxidant like vitamin E partially restores expression of proteins altered upon exposure to DPE/DPE vapor.
Conclusions
Our study highlights distinct adverse effects of chronic exposure to DPE/DPE vapor on skin keratinocytes and the potential role of vitamin E in alleviating adverse effects of environmental pollution.
Abbreviations
DPE
Diesel particulate extract
PAHs
Polycyclic aromatic hydrocarbons
MMPs
Matrix metalloproteinases
ROS
Reactive oxygen species
ARE
Antioxidant Response Element
NHEK-Ad
Adult normal human epidermal keratinocytes
ECM
extracellular matrix membrane
HPRD
Human Protein Reference Database
TEABC
Triethyl ammonium bicarbonate
BCA
Bicinchoninic acid
TMT
Tandem Mass Tag
NADPH
Nicotinamide adenine dinucleotide phosphate
HCD
High energy Collision induced Dissociation
AGC
Automatic Gain Control
Keywords
Pollution
Tocopherol
Orbitrap Fusion
Quantitative proteomics
Skin keratinocytes
Electron transport chain
KBJ00000000009383
2018-09-18T19:52:37
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