Effects of Acrolein on the Proliferation of and Per1 Gene Expression in Pulmonary Epithelial Cells

LI Cong-min, LIU Yang, XU Li-min, WU Wei-dong, JIANG Bi-jie

Abstract

To investigate the effect of acrolein on the proliferation of pulmonary epithelial cells and its possible mechanism.  Methods  Two strains of pulmonary epithelial cells, A549 cells and MLE15 cells, were used as in vitro models of pulmonary epithelial cell, and were treated with 80 μmol/L acrolein or phosphate buffer saline (PBS) as the control. The proliferation of pulmonary epithelial cells were determined with CCK-8 kit after cell culturing resumed for 12 h, 24 h, 36 h and 48 h post acrolein treatment, and the expression of period circadian regulator gene 1 (Per1) was examined using Western blot test 24 h after acrolein treatment. In addition, after acrolein treatment, the cells were restored with transforming growth factor-β (TGF-β) added in the medium, and the cell proliferation and the expression of Per1 protein were also examined.  Results  The proliferation of A549 cells and MLE15 cells decreased significantly after being treated with 80 μmol/L acrolein for 30 min, and the expression of Per1 protein was also downregulated significantly (P<0.05). The addition of TGF-β after acrolein treatment did not significantly change the reduction in cell proliferation caused by acrolein, but the expression of Per1 protein in pulmonary epithelial cells was significantly higher than that in cells restored without TGF-β (P<0.05). Conclusion Acrolein treatment resulted in the decreased proliferation of pulmonary epithelial cells and the Per1 expression in pulmonary epithelial cells. Although TGF-β addition did not reverse the reduction of cell proliferation after acrolein treatment, the Per1 expression levels were recovered to a certain extent compared to that in cells restored in medium without TGF-β after acrolein treatment.

 

Keywords: Acrolein, Pulmonary epithelial cells, Per1, Transforming growth factor-β

 

Full Text:

PDF


References


CONKLIN D J， HABERZETTL P， JAGATHEESAN G， et al. Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein. Toxicol Appl Pharmacol，2017，324: 61–72.

GIBBS-FLOURNOY E A， GILMOUR M I， HIGUCHI M， et al. Differential exposure and acute health impacts of inhaled solid-fuel emissions from rudimentary and advanced cookstoves in female CD-1 mice. Environ Res，2018，161: 35–48.

SIERRA L M， BARROS A R， GARC A M， et al. Acrolein genotoxicity in Drosophila melanogaster.Ⅰ. Somatic and germinal mutagenesis under proficient repair conditions. Mutat Res，1991，260(3): 247–256.

SHI R， RICKETT T， SUN W. Acrolein-mediated injury in nervous system trauma and diseases. Mol Nutr Food Res，2011，55(9): 1320–1331.

YEAGER R P， KUSHMAN M， CHEMERYNSKI S， et al. Proposed mode of action for acrolein respiratory toxicity associated with inhaled tobacco smoke. Toxicol Sci，2016，151(2): 347–364.

HENNING R J， JOHNSON G T， COYLE J P， et al. Acrolein can cause cardiovascular disease: a review. Cardiovasc Toxicol，2017，17(3): 227–236.

KWOLEK-MIREK M， ZADRĄG-TĘCZA R， BEDNARSKA S， et al. Acrolein-induced oxidative stress and cell death exhibiting features of apoptosis in the yeast Saccharomyces cerevisiae deficient in SOD1. Cell BiochemBiophys，2015，71(3): 1525–1536.

RIE M， NAOYUKI T， HIROSHI S， et al. Circadian rhythms of oxidative stress markers and melatonin metabolite in patients with xeroderma pigmentosum group A. Oxid Med Cell Longev， 2016， 2016: 5741517[2019-12-14]. https://doi.org/10.1155/2016/5741517.

WU X， CHEN L， ZEB F， et al. Clock-Bmal1 mediates MMP9 induction in acrolein-promoted atherosclerosis associated with gut microbiota regulation. Environ Pollut，2019，252(Pt B): 1455–1463.

SUNDAR I K， YAO H， SELLIX M T， et al. Circadian clock coupled lung cellular and molecular functions in chronic airway diseases. Am J Respir Cell Mol Biol，2015，53(3): 285–290.

MAUVOISIN D. Circadian rhythms and proteomics: it's all about posttranslational modifications. Wiley Interdiscip Rev Syst Biol Med， 2019， 11(5): e1450[2020-04-27].https://doi.org/10.1002/wsbm.1450.

SAITO A， HORIE M， NAGASE T. TGF-beta signaling in lung health and disease. Int J Mol Sci， 2018， 19(8): pii: E2460[2019-12-14]. https://doi.org/10.3390/ijms19082460.

BOGUSŁAWSKA J， RODZIK K， POPŁAWSKI P， et al. TGF-β1 targets a microRNA network that regulates cellular adhesion and migration in renal cancer. Cancer Lett，2020，480: 52–55.

GUAN S， ZHOU J. CXCR7 attenuates the TGF-beta-induced endothelial-to-mesenchymal transition and pulmonary fibrosis. Mol Biosyst，2017，13(10): 2116–2124.

HAGIMOTO N， KUWANO K， INOSHIMA I， et al. TGF- 1 as an enhancer of Fas-mediated apoptosis of lung epithelial cells. J Immunol， 2002，168(12): 6470–6478.

GU L Z， SUN H， CHEN J H. Histone deacetylases 3 deletion restrains PM2.5-induced mice lung injury by regulating NF-kappaB and TGF-beta/Smad2/3 signaling pathways. Biomed Pharmacother，2017，85: 756–762.

EUA. Department of Health and Human Services. Agency for Toxic Substances and Disease Registry. Toxicological profile for acrolein. Atlanta: Agency for Toxic Substances and Disease Registry， 2007: 1−5.

MARANO F， PUISEUX-DAO S. Acrolein and cell cycle. Toxicol Lett， 1982，14(3/4): 143–149.

SUN Y， ITO S， NISHIO N， et al. Acrolein induced both pulmonary inflammation and the death of lung epithelial cells. Toxicol Lett，2014， 229(2): 384–392.

LAU S， RANGARAJAN R， PHILIDET C， et al. Effects of acrolein in comparison to its prodrug cyclophosphamide on human primary endothelial cells in vitro. Toxicol In Vitro， 2020， 62: 104685[2019-12-14]. https://doi.org/10.1016/j.tiv.2019.104685.

JANG J H， BRUSE S， HUNEIDI S， et al. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein. Environ Health Perspect，2014，122(9): 955–962.

HORTON N D， BISWAL S S， CORRIGAN L L， et al. Acrolein causes inhibitor kappaB-independent decreases in nuclear factor kappaB activation in human lung adenocarcinoma (A549) cells. J Biol Chem， 1999，274(14): 9200–9206.

PARK J H， KU H J， LEE J H. et al. IDH2 deficiency exacerbates acrolein-induced lung injury through mitochondrial redox environment deterioration. Oxid Med Cell Longev， 2017， 2017: 1595103[2020-04-27]. https://doi.org/10.1155/2017/1595103.

ZHANG S， ZHANG J， CHEN H， et al. Combined cytotoxicity of co-exposure to aldehyde mixtures on human bronchial epithelial BEAS-2B cells. Environ Pollut，2019，250: 650–661.

HERNÁNDEZ-ROSAS F， LÓPEZ-ROSAS C A， SAAVEDRA-VÉLEZ M V. Disruption of the molecular circadian clock and cancer: an epigenetic link. Biochem Genet，2020，58(1): 189–209.

SUNDAR I K， YAO H， SELLIX M T， et al. Circadian molecular clock in lung pathophysiology. Am J Physiol Lung Cell Mol Physiol，2015， 309(10): L1056–L1075.

SONG P， LI Z， LI X， et al. Transcriptome profiling of the lungs reveals molecular clock genes expression changes after chronic exposure to ambient air particles. Int J Environ Res Public Health， 2017， 14(1): pii: E90[2020-04-27].https://doi.org/10.3390/ijerph14010090.

GOPAL S， VERACINI L， GRALL D， et al. Fibronectin-guided migration of carcinoma collectives. Nat Commun， 2017， 8: 14105[2019-12-14]. https://www.nature.com/articles/ncomms14105. doi: 10.1038/ncomms14105.

LEASK A. Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ Res，2010，106(11): 1675–1680.

DENG Y L， XIONG X Z， CHENG N S. Organ fibrosis inhibited by blocking transforming growth factor-β signaling via peroxisome proliferator-activated receptor γ agonists. Hepatobiliary Pancreat Dis Int， 2012，11(5): 467–478.

GAO H， BO Z， WANG Q， et al. Salvanic acid B inhibits myocardial fibrosis through regulating TGF-β1/Smad signaling pathway. Biomed Pharmacother，2019，110: 685–691.

WANG J， SHEN W， ZHANG J Y， et al. Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-β1/Smad signaling pathway. Food Funct， 2019，10(2): 1179–1190.

ASCHNER Y， DOWNEY G P. Transforming growth factor-β: master regulator of the respiratory system in health and disease. Am J Respir Cell Mol Biol，2016，54(5): 647–655.

ZIYADEH F N. Mediators of diabetic renal disease: the case for TGF-beta as the major mediator. J Am Soc Nephrol，2004，15 Suppl 1: S55–S57.

GOPAL S， VERACINI L， GRALL D， et al. Fibronectin-guided migration of carcinoma collectives. Nat Commun， 2017， 8: 14105[2020-04-27]. https://www.nature.com/articles/ncomms14105. doi: 10.1038/ncomms14105.


Refbacks

  • There are currently no refbacks.