Urban air particulate matter induces mitochondrial dysfunction in human olfactory mucosal cells.
Aged
Air Pollutants
/ toxicity
Animals
Apoptosis
/ drug effects
C-Reactive Protein
/ genetics
Cell Culture Techniques
Cells, Cultured
Cities
Cytokines
/ metabolism
Humans
Inflammation
Male
Membrane Potential, Mitochondrial
/ drug effects
Middle Aged
Mitochondria
/ drug effects
Nerve Tissue Proteins
/ genetics
Olfactory Mucosa
/ drug effects
Oxidative Stress
/ drug effects
Particle Size
Particulate Matter
/ toxicity
Transcriptome
/ drug effects
Urbanization
Air pollution
Inflammation
Mitochondria
NPTX1
olfactory system
oxidative stress
particulate matter
Journal
Particle and fibre toxicology
ISSN: 1743-8977
Titre abrégé: Part Fibre Toxicol
Pays: England
ID NLM: 101236354
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
17
10
2019
accepted:
20
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
2
4
2021
Statut:
epublish
Résumé
The adverse effects of air pollutants including particulate matter (PM) on the central nervous system is increasingly reported by epidemiological, animal and post-mortem studies in the last decade. Oxidative stress and inflammation are key consequences of exposure to PM although little is known of the exact mechanism. The association of PM exposure with deteriorating brain health is speculated to be driven by PM entry via the olfactory system. How air pollutants affect this key entry site remains elusive. In this study, we investigated effects of urban size-segregated PM on a novel cellular model: primary human olfactory mucosal (hOM) cells. Metabolic activity was reduced following 24-h exposure to PM without evident signs of toxicity. Results from cytometric bead array suggested a mild inflammatory response to PM exposure. We observed increased oxidative stress and caspase-3/7 activity as well as perturbed mitochondrial membrane potential in PM-exposed cells. Mitochondrial dysfunction was further verified by a decrease in mitochondria-dependent respiration. Transient suppression of the mitochondria-targeted gene, neuronal pentraxin 1 (NPTX1), was carried out, after being identified to be up-regulated in PM Key mitochondrial functions were perturbed by urban PM exposure in a physiologically relevant cellular model via a mechanism involving NPTX1. In addition, inflammatory response and early signs of apoptosis accompanied mitochondrial dysfunction during exposure to PM. Findings from this study contribute to increased understanding of harmful PM effects on human health and may provide information to support mitigation strategies targeted at air pollution.
Sections du résumé
BACKGROUND
The adverse effects of air pollutants including particulate matter (PM) on the central nervous system is increasingly reported by epidemiological, animal and post-mortem studies in the last decade. Oxidative stress and inflammation are key consequences of exposure to PM although little is known of the exact mechanism. The association of PM exposure with deteriorating brain health is speculated to be driven by PM entry via the olfactory system. How air pollutants affect this key entry site remains elusive. In this study, we investigated effects of urban size-segregated PM on a novel cellular model: primary human olfactory mucosal (hOM) cells.
RESULTS
Metabolic activity was reduced following 24-h exposure to PM without evident signs of toxicity. Results from cytometric bead array suggested a mild inflammatory response to PM exposure. We observed increased oxidative stress and caspase-3/7 activity as well as perturbed mitochondrial membrane potential in PM-exposed cells. Mitochondrial dysfunction was further verified by a decrease in mitochondria-dependent respiration. Transient suppression of the mitochondria-targeted gene, neuronal pentraxin 1 (NPTX1), was carried out, after being identified to be up-regulated in PM
CONCLUSION
Key mitochondrial functions were perturbed by urban PM exposure in a physiologically relevant cellular model via a mechanism involving NPTX1. In addition, inflammatory response and early signs of apoptosis accompanied mitochondrial dysfunction during exposure to PM. Findings from this study contribute to increased understanding of harmful PM effects on human health and may provide information to support mitigation strategies targeted at air pollution.
Identifiants
pubmed: 32487172
doi: 10.1186/s12989-020-00352-4
pii: 10.1186/s12989-020-00352-4
pmc: PMC7268298
doi:
Substances chimiques
Air Pollutants
0
Cytokines
0
Nerve Tissue Proteins
0
Particulate Matter
0
neuronal pentraxin
0
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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