The effects of ceruloplasmin in PI3K/PTEN cell signaling pathway change induced by silica.
- Author:
Xianan ZHANG
1
;
Yuegang LI
1
;
Xiaowei JIA
1
;
Bingci LIU
1
;
Meng YE
2
Author Information
- Publication Type:Journal Article
- MeSH: Cell Proliferation; drug effects; Cells, Cultured; Ceruloplasmin; pharmacology; Class Ia Phosphatidylinositol 3-Kinase; metabolism; Fibroblasts; drug effects; metabolism; Humans; PTEN Phosphohydrolase; metabolism; Signal Transduction; drug effects; Silicon Dioxide; toxicity
- From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2014;32(4):241-245
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the roles of ceruloplasmin (Cp) in PI3K/PTEN cell signaling pathway change in human embryonic lung fibroblasts (HELFs) induced by silica.
METHODSHELFs transfected with pGenesil1.1 plasmid and pGenesil1.1 with PTEN shRNA (PT) plasmid were successfully established. 100 µg/ml silica and different concentrations of Cp (10, 20, 30 µg/ml) were used in this experiment and Cp were treated cells after exposed to silica for 1h. Three different cell lines (including HELFs, PT and cells were transfected with p85 dominant negative mutant plasmid (DN-p85)) were divided into control groups, silica groups and silica+different concentrations of Cp groups. MTT assay was used to detect the effects of Cp on silica-induced cell proliferation after inhibiting PTEN and p85. When suppressing the expression of PTEN and p85, western blot assay was performed to detect the levels of p85, p110, AKT308, AKT473 and ERK, JNK and their phosphorylated levels.
RESULTSAfter inhibition of PTEN, the high levels of p85 induced by 100 µg/ml silica with 30 µg/ml Cp were markedly decreased (P<0.05). When suppressing p85, the increased cell proliferation was not observed. And the high levels of AKT308, AKT473, ERK and phosphorylated JNK and ERK stimulated by 100 µg/ml silica with 30 µg/ml Cp were decrease (P < 0.05).
CONCLUSIONCp could further strengthened silica-induced cell proliferation by PI3K/AKT/MAPK cell signaling pathway, of which the level of p85 was regulated by PTEN.