Cytoplasmic p21^CIP1/WAF1, ERK1/2 activation, and cytoskeletal remodeling are associated with the senescence-like phenotype after airborne particulate matter (PM₁₀) exposure in lung cells

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• 作者：Yesennia S谩nchez-P茅rez ; Yol ; a I. Chirino ; 脕lvaro Rom谩n Osornio-Vargas ; Luis A. Herrera ; Roc铆o Morales-B谩rcenas ; Alej ; ro L贸pez-Saavedra ; Imelda Gonz谩lez-Ram铆rez ; Javier Mir ; a ; Claudia Mar铆a Garc铆a-Cuellar
• 关键词：Particulate matter ; PM10 ; Cytoskeleton remodeling ; p21CIP1/WAF1 cytoplasmic ; Senescence-like
• 刊名：Toxicology Letters
• 出版年：10 February, 2014
• 年：2014
• 卷：225
• 期：1
• 页码：12-19
• 全文大小：1742 K

文摘

The exposure to particulate matter with a mean aerodynamic diameter 鈮?0 渭m (PM₁₀) from urban zones is considered to be a risk factor in the development of cancer. The aim of this work was to determine if PM₁₀ exposure induces factors related to the acquisition of a neoplastic phenotype, such as cytoskeletal remodeling, changes in the subcellular localization of p21^CIP1/WAF1, an increase in 尾-galactosidase activity and changes in cell cycle. To test our hypothesis, PM₁₀ from an industrial zone (IZ) and a commercial zone (CZ) were collected, and human adenocarcinoma lung cell cultures (A549) were exposed to a sublethal PM₁₀ concentration (10 渭g/cm²) for 24 h and 48 h. The results showed that PM₁₀ exposure induced an increase in F-actin stress fibers and caused the cytoplasmic stabilization of p21^CIP1/WAF1 via phosphorylation at Thr¹⁴⁵ and Ser¹⁴⁶ and the phosphorylation of ERK1/2 on Thr²⁰². Changes in the cell cycle or apoptosis were not observed, but an increase in 尾-galactosidase activity was detected. The PM₁₀ from CZ caused more dramatic effects in lung cells. We conclude that PM₁₀ exposure induced cytoplasmic p21^CIP1/WAF1 retention, ERK1/2 activation, cytoskeleton remodeling and the acquisition of a senescence-like phenotype in lung cells. These alterations could have mechanistic implications regarding the carcinogenic potential of PM₁₀.