Urban air particulate matter induces mitochondrial dysfunction in human olfactory mucosal cells
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Lampinen, Riikka
Saveleva, Liudmila
Korhonen, Paula
Mikhailov, Nikita
Grubman, Alexandra
Polo, Jose M
Wilson, Trevor
Komppula, Mika
Ronkko, Teemu
Gu, Cheng
Mackay-Sim, Alan
Malm, Tarja
White, Anthony R
et al.
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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 PM2.5-1 treated cells via RNA sequencing. Suppression of NPTX1 in cells exposed to PM did not restore mitochondrial defects resulting from PM exposure. In contrast, PM-induced adverse effects were magnified in the absence of NPTX1, indicating a critical role of this protein in protection against PM effects in hOM cells. 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.
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Particle and Fibre Toxicology
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17
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1
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© The Author(s). 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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Macromolecular and materials chemistry
Medicinal and biomolecular chemistry
Other health sciences
Science & Technology
Life Sciences & Biomedicine
Toxicology
Mitochondria
olfactory system
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Chew, S; Lampinen, R; Saveleva, L; Korhonen, P; Mikhailov, N; Grubman, A; Polo, JM; Wilson, T; Komppula, M; Ronkko, T; Gu, C; Mackay-Sim, A; Malm, T; White, AR; Jalava, P; Kanninen, KM, Urban air particulate matter induces mitochondrial dysfunction in human olfactory mucosal cells, Particle and Fibre Toxicology, 2020, 17 (1), pp. 18