Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells

Heavy metals are important for various biological systems, but, in excess, they pose a serious risk to human health. Heavy metals are commonly used in consumer and industrial products. Despite the increasing evidence on the adverse effects of heavy metals, the detailed mechanisms underlying their action on lung cancer progression are still poorly understood. In the present study, we investigated whether heavy metals (mercury chloride and lead acetate) affect cell viability, cell cycle, and apoptotic cell death in human lung fibroblast MRC5 cells. The results showed that mercury chloride arrested the sub-G1 and G2/M phases by inducing cyclin B1 expression. In addition, the exposure to mercury chloride increased apoptosis through the activation of caspase-3. However, lead had no cytotoxic effects on human lung fibroblast MRC5 cells at low concentration. These findings demonstrated that mercury chloride affects the cytotoxicity of MRC5 cells by increasing cell cycle progression and apoptotic cell death.

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Requirement of Hydrogen Peroxide Generation in TGF-β1 Signal Transduction in Human Lung Fibroblast Cells: Involvement of Hydrogen Peroxide and Ca2+in TGF-β1-Induced IL-6 Expression

The Journal of Immunology ◽

10.4049/jimmunol.165.4.2190 ◽

2000 ◽

Vol 165 (4) ◽

pp. 2190-2197 ◽

Cited By ~ 106

Author(s):

Eunsung Junn ◽

Kee Nyung Lee ◽

Hyang Ran Ju ◽

Seung Hyun Han ◽

Joo Young Im ◽

...

Keyword(s):

Signal Transduction ◽

Hydrogen Peroxide ◽

Human Lung ◽

Lung Fibroblast ◽

Fibroblast Cells ◽

Human Lung Fibroblast ◽

Hydrogen Peroxide Generation ◽

Tgf Β1

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Heat shock protein 27 promotes cell cycle progression by down-regulating E2F transcription factor 4 and retinoblastoma family protein p130

Journal of Biological Chemistry ◽

10.1074/jbc.ra118.003310 ◽

2018 ◽

Vol 293 (41) ◽

pp. 15815-15826 ◽

Cited By ~ 5

Author(s):

Ah-Mee Park ◽

Ikuo Tsunoda ◽

Osamu Yoshie

Keyword(s):

Cell Cycle ◽

Heat Shock ◽

Heat Shock Protein ◽

Cellular Senescence ◽

Cell Cycle Progression ◽

Heat Shock Protein 27 ◽

Serum Starvation ◽

Cell Cycle Gene ◽

Cycle Progression ◽

Human Lung Fibroblast

Heat shock protein 27 (HSP27) protects cells under stress. Here, we demonstrate that HSP27 also promotes cell cycle progression of MRC-5 human lung fibroblast cells. Serum starvation for 24 h induced G1 arrest in these cells, and upon serum refeeding, the cells initiated cell cycle progression accompanied by an increase in HSP27 protein levels. HSP27 levels peaked at 12 h, and transcriptional up-regulation of six G2/M-related genes (CCNA2, CCNB1, CCNB2, CDC25C, CDCA3, and CDK1) peaked at 24–48 h. siRNA-mediated HSP27 silencing in proliferating MRC-5 cells induced G2 arrest coinciding with down-regulation of these six genes. Of note, the promoters of all of these genes have the cell cycle–dependent element and/or the cell cycle gene-homology region. These promoter regions are known to be bound by the E2F family proteins (E2F-1 to E2F-8) and retinoblastoma (RB) family proteins (RB1, p107, and p130), among which E2F-4 and p130 were strongly up-regulated in HSP27-knockdown cells. E2F-4 or p130 knockdown concomitant with the HSP27 knockdown rescued MRC-5 cells from G2 arrest and up-regulated the six cell cycle genes. Moreover, we observed cellular senescence in MRC-5 cells on day 3 after the HSP27 knockdown, as evidenced by increased senescence-associated β-gal activity and up-regulated inflammatory cytokines. The cellular senescence was also suppressed by the concomitant knockdown of E2F-4/HSP27 or p130/HSP27. Our findings indicate that HSP27 promotes cell cycle progression of MRC-5 cells by suppressing expression of the transcriptional repressors E2F-4 and p130.

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