Benzo (a) pyrene-induced human embryo lung cell cycle alterations through positive regulation of mitogen-activated protein kinase signal pathways.
- Author:
Hong-ju DU
1
;
Ning TANG
;
Bing-ci LIU
;
Xiang-lin SHI
;
Chuan-shu HUANG
;
Ai GAO
;
Fu-hai SHEN
;
Meng YE
;
Bao-rong YOU
Author Information
- Publication Type:Journal Article
- MeSH: Benzo(a)pyrene; toxicity; Cell Cycle; drug effects; Cells, Cultured; Fibroblasts; drug effects; metabolism; Humans; JNK Mitogen-Activated Protein Kinases; metabolism; Lung; cytology; embryology; MAP Kinase Kinase 4; metabolism; MAP Kinase Signaling System; drug effects; Mitogen-Activated Protein Kinase 1; metabolism; Mitogen-Activated Protein Kinase 3; metabolism; Mitogen-Activated Protein Kinase 8; metabolism; Mitogen-Activated Protein Kinase 9; metabolism; Signal Transduction; drug effects; p38 Mitogen-Activated Protein Kinases; metabolism
- From: Chinese Journal of Preventive Medicine 2007;41(4):277-280
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the effects of benzo(a)pyrene (BaP) on the cell cycle distribution and activities of mitogen-activated protein kinase (MAPK) signal molecules (ERK1/2, JNK1/2 and p38) in human embryo lung cells (HELF), and to investigate the relationship between alterations of MAPK protein phosphorylation and the cell cycle distributions.
METHODSThe phosphorylation of MAPK were induced by exposing HELF cells to BaP at 0.1, 0.5, 2.5 and 12.5 micromol/L. The phosphorylation and protein expression levels of ERK1/2, JNK1/2 and p38 were determined through western-blotting assay. And the flow cytometry assay was used to measure the cell cycle effects in HELF cells after treatment with 2.5 micromol/L BaP for 24 h.
RESULTSThe phosphorylation levels of ERK1/2, JNK1/2 and p38 were significantly increased through BaP exposure. In addition, the phosphorylation of these three MAPKs has similar alteration pattern. We found that exposure of cells to 2.5 microM of BaP for 24 h resulted in a decrease of G(0) and G(1) population by 11.9% (F = 41.38, P < 0.01) and an increase of S population by 17.2% (F = 68.13, P < 0.01). Three chemical inhibitors of MAPK (AG126, SP600125 and SB203580) could significantly inhibit the cell cycle alteration because of BaP treatment.
CONCLUSIONERK1/2, JNK1/2 and p38 could positively regulate the BaP independently induced cell cycle alterations.
