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Oxidative stress and cell cycle arrest induced by short-term exposure to dustfall PM2.5 in A549 cells

  • Interface Effect of Ultrafine Mineral Particles and Microorganisms
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Abstract

It was reported that in vitro short-term exposure to PM2.5 caused different lung diseases through inflammatory response, immune toxicity, oxidative stress, and genetic mutations. However, the complex molecular biological mechanism for its toxicity had not been fully elucidated. Therefore, the present study investigated the cytotoxicity, oxidative damage, mitochondria damage, apoptosis, and cell cycle arrest of NX and QH PM2.5 in A549 cells. Further, cell cycle arrest-related gene levels in PM2.5-induced A549 cells were also detected. Our results suggested that PM2.5 reduced the cell viability in A549 cells. Simultaneously, excessive ROS decreased MMP levels and damaged mitochondrial membrane integrity and induced mitochondrial oxidative damage through the oxygen-dependent killer route, resulting in mitochondrial damage and cell apoptosis. Besides, the results also showed that PM2.5 induced A549 cell cycle alteration in G2/M phase after co-culture for 24 h. G2/M phase arrest was induced by upregulation of p53 and p21 and downregulation of CDK1 mRNA expression. In addition, lncRNA Sox2ot might play an important role as the specific oncogenes and it participated in G2/M phase arrest by regulating the expression of EZH2.

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Abbreviations

ATP:

Adenosine triphosphate

CKI:

Cyclin-dependent kinase Inhibitor

CDKs:

Cyclin-dependent kinases

DCF:

Dichlorofluorescein

DCFH-DA:

2′,7′-Dichlorofluorescein diacetate

DMSO:

Dimethyl sulfoxide

EZH2 :

Enhancer of zeste homolog 2

FBS:

Fetal bovine serum

H3K27me3 :

Histone H3 lysine 27 trimethylation

IARC:

International Agency for Research on Cancer

JC-1:

5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-benzimidazolylcarbocyanine iodide

lncRNA:

Long non-coding RNA

MMP:

Mitochondrial membrane potential

MPTP:

Mitochondrial permeability transition pore

MTT:

3-(4,5-Dimetrylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NRF2 :

NF-E2-related factor 2

NF-κB:

Nuclear factor-kappa B

NX:

Yongning, Ningxia Province, China

OFR:

Oxygen free radicals

PAHs:

Polycyclic aromatic hydrocarbons

PARP:

Poly-ADP-ribose polymerase

PBS:

Phosphate-buffered solution

PCNA:

Proliferating cell nuclear antigen

PI:

Propidium iodide

PM2.5 :

Particulate matter less than 2.5 μm

QH:

Xining, Qinhai Province, China

qRT-PCR:

Quantitative real-time PCR

ROS:

Reactive oxygen species

Sox2ot:

Sox2 overlapping transcript

TNF-α:

Tumor necrosis factor-α

UV:

Ultraviolet

VOCs:

Volatile organic compounds

XRD:

X-ray diffraction

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Acknowledgments

This research was funded by the National Natural Fund Project of China (No. 41472046; No. 41602033) and the Science and Technology Project of Sichuan Province, China (No. 2016JY0045).

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Authors and Affiliations

  1. Department of Clinical Laboratory, Southwest Medical University, Luzhou, Sichuan Province, 646000, China

    Jie Yang, Yulin Wang & Jianjun Deng

  2. School of Environmental Resource and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan Province, 621003, China

    Tingting Huo, Jie Ma & Faqin Dong

  3. Medical Laboratory, Sichuan Mianyang 404 hospital, No.2 Affiliated Hospital of North Sichuan Medical College, Mianyang, Sichuan Province, 621000, China

    Xu Zhang & Jianjun Deng

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  1. Jie Yang
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  2. Tingting Huo
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Correspondence to Jianjun Deng.

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Yang, J., Huo, T., Zhang, X. et al. Oxidative stress and cell cycle arrest induced by short-term exposure to dustfall PM2.5 in A549 cells. Environ Sci Pollut Res 25, 22408–22419 (2018). https://doi.org/10.1007/s11356-017-0430-3

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